Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: Figure 1 with 3 supplements see all Download asset Open asset L. plantarum can reduce both Fe3+ and an anode through EET. (A) Reduction of Fe3+ (ferrihydrite) to Fe2+ by L. plantarum NCIMB8826 after growth in mMRS. The assays were performed in PBS supplemented with 20 µg/mL DHNA and/or 55 mM mannitol. Fe2+ was detected colorimetrically using 2 mM ferrozine. For L. plantarum inactivation, cells were incubated at 85℃ in PBS for 30 min prior to the assay. Significant differences were determined by one-way ANOVA with Tukey’s post-hoc test (n = 3), *** p < 0. 001. (B) Two-chambered electrochemical cell setup for measuring current generated by L. plantarum. (C) Current density production over time by L. plantarum in CDM supplemented with 20 µg/mL DHNA and/or 110 mM mannitol. The anode was polarized at +0. 2VAg/AgCl. The avg ± stdev of three biological replicates is shown. See also Figure 1—figure supplement 1 and Figure 1—figure supplement 2 and related data in Figure 1—source data 1. Figure 1—source data 1 Raw data of Figure 1A and B. Download elife-70684-fig1-data1-v2. xlsx Next, we investigated whether the ability of L. plantarum to reduce insoluble iron was altered by growth media. L. plantarum was able to reduce iron after growth in either complete (MRS) medium or chemically defined medium (CDM) (Figure 1—figure supplement 1B). Iron reduction was greater when mannitol, a sugar alcohol, rather than glucose, was provided as the sole carbon source in MRS (Figure 1—figure supplement 1B). However, reduction was highest when L. plantarum was incubated in mannitol-containing MRS (mMRS) with both DHNA and ferric ammonium citrate present (Figure 1—figure supplement 1D). The addition of riboflavin to the growth medium did not further increase iron reduction by L. [SEP] Justify:

Output: The text does not directly address the claim regarding the importance of lactic acid bacteria in fermentation processes. Instead, it focuses on the specific activities of L. plantarum, such as its ability to reduce iron in different growth media, without mentioning fermentation or its significance in that context.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: It is possible that environments that have been habitable for far longer than Earth may never develop complex life with multicellular organisms. We cannot know with certainty, as we are still uncovering how life transitioned from entirely unicellular and microscopic to complex, multicellular life on Earth (see 5. 4. 3). Discussion of the many factors affecting planetary habitability is expanded in the supplementary material. 7. 2. Considerations for Habitable EnvironmentsThus far, the only known habitable environments are found on Earth. However, there are a number of potentially habitable environments scattered throughout the Solar System, many of which currently or in the past could resemble extreme environments on Earth (see 6. 3). The rocky planets Mars and Venus are especially compelling targets for understanding habitability due to their similarity in size and location to Earth. There are several examples within the of uninhabitable planets with potentially habitable moons. The study of extrasolar planets and their parent stars also informs us about the formation and evolution of potentially habitable worlds. The similarity of planetary processes among diverse star systems suggests that moons orbiting exoplanets (i. e. , exomoons; Teachey and Kipping, 2018) are also worthy of consideration as potentially habitable environments, although no such bodies have been observed to date. This section covers the state of our current understanding of the potential habitability of extraterrestrial environments in the and beyond. Several key bodies are the subjects of spacecraft missions in progress or in development: Mars (7. 2. 1), Venus (7. 2. 2), Europa (7. 2. 3), Titan (7. 2. 5), Ganymede (7. 2. 6), and exoplanets (7. 2. 10). These bodies are focal points of research activity and funding opportunities. We cover numerous other bodies because they have significance to the field of astrobiology even if they are not thought to be habitable. 7. 2. 1. MarsSystem bodies, Mars has received by far the most attention in the search for life beyond Earth. Exploration of Mars by multiple orbital and landed spacecraft has characterized global trends in the evolution of climate, aqueous activity, and geochemistry. Scientific consensus has tended toward less habitable surface conditions as the evolution of Mars progressed. In-depth exploration of Meridiani Planum, Gusev crater, and Gale crater by the rovers Opportunity (Arvidson et al. [SEP] Justify:

Output: The text corroborates the claim by discussing the potential habitability of environments beyond Earth and highlighting the research focused on locations such as Mars, Venus, and various celestial bodies. It emphasizes the ongoing exploration to understand planetary habitability and the conditions that may lead to life beyond our planet, which directly aligns with the field of astrobiology.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: Skip to Content eLife home page your research Search by keyword or author Reset form my search to Research 10. 7554/eLife. 89386. 2 Open access Copyright information Version of RecordDecember 22, 2023 Read the peer reviews Reviewed preprintAugust 8, 2023 Open annotations (there are currently 0 annotations on this page). 7,382 views 560 downloads 44 9386. Copy to clipboard Download BibTeX Download. RIS Full text Figures and data Peer review Side by side Peer review process #1 (Public Review): Reviewer #2 (Public Review): Author response Peer review process Version of Record: This is the final version of the 2. While the authors list their limited number of docking methods as a caveat, the fact that they use three state-of-the-art ligand docking methods is a strength of the work; many studies use just one. The rigorous analysis of the binding site RMSD and docked ligand pose RMSD is novel to my knowledge and is particularly insightful. Weaknesses: The authors are rigorous in their approach by using state-of-the-art workflows that are high-throughput in nature. However, human expert-refined models and expert selection from multiple models could improve the results of ligand pose prediction when using protein models. The authors alluded to this for traditional models but this can also be true when starting from AF2 models. This is difficult to test systematically and rigorously, however. One possible experiment is to explore whether using multiple AF2 models (there are five by default) would have an effect on pose accuracy, perhaps for selected examples such as NK1R, 5HT2A, and DRD1 to help build out the discussion further. Another possible weakness is that the authors focus only on GPCRs for reasons they state but make a good argument as to why the conclusions are likely to extend to other protein classes. Context: One of the most common and impactful uses of protein structures is in small molecule therapeutic chemical tool design. When no experimental structure is available, models are frequently used and such models include traditional template-based homology models and, more recently, AF2 models. AF2 is widely recognized as an inflection point in protein structure prediction due to the unprecedented accuracy of the protein structure models produced automatically. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of current protein structure models, particularly noting that while the authors utilize advanced docking methods, there are still weaknesses that could affect accuracy. The text mentions that traditional models and even the newer AF2 models can benefit from human expert refinement, which implicitly suggests that not all models—be they economic or biophysical—can accurately predict behavior due to inherent limitations.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: plantarum (Figure 1—figure supplement 1E), potentially because riboflavin is already present in high quantities in MRS, a medium containing yeast extract (Tomé, 2021). Thus, L. plantarum was grown in mMRS supplemented with DHNA and iron before ferrihydrite reduction assays in all subsequent experiments. L. plantarum EET activity was confirmed in a bioelectrochemical reactor by quantifying electron output as current (Figure 1B). L. plantarum reduced a carbon electrode (anode) polarized to +200 mVAg/AgCl in the presence of both DHNA and an electron donor (mannitol) (Figure 1C). No current was observed in the absence of L. plantarum (Figure 1—figure supplement 2A), indicating that current production stems from a biological process. L. plantarum produced a maximum current of 129 ± 19 µA/cm2 in mCDM (Figure 1C) and 225 ± 9 µA/cm2 in mMRS (Figure 1—figure supplement 2B). Under EET conditions in mCDM, the L. plantarum biomass was 2. 7 mg (dry cell mass). Assuming 50% of the dry cell mass was protein, the specific electron transfer rate was 57 µmol electrons/mg- protein/hr and the current production was 1. 5 mA/mg-protein. This value is lower than that reported for Geobacter sulfurrenducens (4–8 mA/mg-protein) (Marsili et al. , 2010; Rose and Regan, 2015), the model species for direct EET, and higher than that of Shewanella oneidensis (0. 67 mA/mg-protein) (Marsili et al. , 2008), the model species for mediated EET. It should be noted that these species, unlike L. plantarum, can synthesize riboflavin and quinones and do not require the addition of either for EET activity. Similar to our iron reduction experiments, EET to an anode occurred with different electron donors and growth media (Figure 1—figure supplement 2B-C), and current increased after supplementation of riboflavin when it was omitted from the growth medium (Figure 1—figure supplement 2D). Because of these differences, CDM was amended with mannitol and riboflavin in subsequent experiments. [SEP] Justify:

Output: The text does not directly address the importance of lactic acid bacteria in fermentation processes. Instead, it focuses on the electron transfer activity of L. plantarum under specific experimental conditions and its comparisons with other bacteria. Therefore, the text is deemed irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: , 2014), Spirit (Ruff et al. , 2020), and Curiosity (Grotzinger et al. , 2014), respectively, has revealed regional and temporal variability in the potential habitability of the martian surface and near subsurface. Mars, like Earth, has hosted a wide diversity of environments that offer clues to understanding the habitability of Mars now or in the past. 7. 2. 1. 1. Global trends in climate and aqueous activityWhile volcanically generated basalt is the predominant type of rock on the martian surface, there is also evidence for the presence of liquid water throughout most of its history, with decreasing frequency through time (Kite, 2019). Because the presence of surface liquid water is critical for the habitability of a planetary surface, the climate has largely dictated the long-term surface habitability of Mars. The subsurface habitability of Mars is also dictated by climate, which impacts the crustal depths at which ice versus liquid water is stable, as well as the geochemical characteristics of any subsurface liquid water (7. 1. 3 in the supplementary material). The climate of ancient Mars and the geochemical characteristics of surface and subsurface water can be determined by studying the geologic record of Mars. The history of Mars is broken into three major eras (Fig. 7. 2): Noachian (4. 1–3. 7 Ga), Hesperian (3. 7–3. 1 Ga), and Amazonian (3. 1 Ga–present), each with different predominant conditions. During the Noachian, significant alteration of primary volcanic deposits formed clay and carbonate minerals on the surface and subsurface of Mars, which required the presence of liquid water (Bibring et al. , 2006). Transient warming episodes are thought to have occurred during the Hesperian, but with a lower frequency compared to the Noachian (Kite, 2019). Under such “warm and wet” periods, fluvial activity (e. g. , erosion by rivers) occurred during the Noachian and was particularly heightened during the Noachian–Hesperian transition (based on the relatively large number of fluvial channels visible in Noachian terrains from orbit; Fassett and Head, 2008). [SEP] Justify:

Output: The text supports the claim by discussing the habitability of Mars, which is directly related to astrobiology's focus on the potential for life beyond Earth. It explains how diverse environments on Mars and the evidence of liquid water contribute to understanding the possibility of past or present life, aligning with the central theme of astrobiology.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: However, understanding whether this unprecedented accuracy translates to better small molecule ligand pose prediction has been an open question, and this study directly addresses the question in a systematic, rigorous approach. Reviewer #2 (Public Review): While the question of 'are AlphaFold-predicted structures useful for drug design' has largely seen comparisons of AF versus experimental protein structures, this paper takes a less explored (but perhaps more practically important) angle of 'are AlphaFold-predicted structures any better than the previous generation of homology modeling tools' to the protein-ligand (rigid) docking problem. The conclusions of this work will be of largest interest to the audience less familiar with the precision required for successful rigid docking, while the expert crowd might find them obvious, yet a good summary of results previously shown in the literature. Further work, understanding the structural objectives/metrics that should be placed on future AlphaFold-like models for better pose prediction performance, would greatly expand the practicality of the observations made here. The main conclusion of the paper, that structural accuracy (expressed as RMSD) of the protein model is not a good predictor of the accuracy the model will show in rigid docking protein-ligand pose prediction, is a good reminder of the well-appreciated need for high-quality side chain placements in docking. The expected phenomenon of AlphaFold predicting 'more apo-like structures' is often discussed in the field, and readers should be cautious about drawing conclusions from the rigid (rather than flexible, as in some previous works) docking done here. The authors have very clearly communicated that the use of AlphaFold-generated structures in traditional docking might not be a good idea, and motivated that the time of a molecular designer might be better spent preparing a high-quality homology model. The visual presentation of the conclusions is very clear but might leave the reader wanting a more in-depth discussion of which structural elements of the AF models lead to bad docking outcomes. For example, Fig. 3 presents an example of a very accurate AlphaFold prediction leading to the ligand being docked completely outside of the binding pocket. Close inspection of the Figure suggests a clash of the ligand with the slightly displaced tryptophan residue in the AF model that might be to blame, as can be confirmed by comparison of the model and PDB structure by the reader themselves but has not been discussed by the authors. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of AlphaFold-generated protein structures in accurately predicting outcomes in rigid docking experiments. It emphasizes that the structural accuracy of a protein model does not reliably predict the accuracy of docked protein-ligand interactions, thus illustrating that not all models (in this case, AlphaFold) can accurately reflect real-world behavior in drug design contexts.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: plantarum, Lactiplantibacillus pentosus, Lacticaseibacillus rhamnosus, Lacticaseibacillus casei, Enterococcus faecium, and Enterococcus faecalis are capable of Fe3+ reduction (Figure 2B). The genomes of those species also contain a complete FLEET locus (Figure 2A and Figure 2—figure supplement 1). Conversely, strains of Lactococcus lactis, Ligilactobacillus murinus, Levilactobacillus brevis, Pediococcus pentosaceus, and Streptococcus agalactiae showed little to no iron reduction activity (Figure 2B). The presence of FLEET-associated genes varied between those species, but only strains of species found to contain both ndh2, a predicted membrane-bound, type-dehydrogenase, and pplA were able to reduce iron under the conditions tested. L. plantarum NCIMB8826 exhibited the highest EET activity resulting in at least 2. 5-fold greater Fe3+ reduction than the other L. plantarum strains (Figure 2B). Remarkably, however, the L. plantarum NCIMB8826 genome and the genomes of 138 other L. plantarum strains queried all harbored a complete FLEET locus including ndh2 and pplA (Figure 2—figure supplement 1 and Figure 2—figure supplement 2A). Among those strains tested for the capacity to reduce Fe3+, L. plantarum NCIMB700965 and 8. 1 could not reduce Fe3+ but possessed all genes in the FLEET pathway. Closer examination of both strains by aligning their FLEET loci with NCIMB8826 revealed unique IS30-family transposons in the intergenic promoter regions spanning ndh2 and pplA (Figure 2—figure supplement 2A). These genes were minimally expressed in L. plantarum NCIMB700965 and 8. 1 in comparison to NCIMB8826 (Figure 2—figure supplement 2B). ndh2 and pplA were also the only two genes in the FLEET gene locus that were induced when L. [SEP] Justify:

Output: The text focuses on the capability of certain lactic acid bacterial strains to reduce Fe3+ and discusses various genetic aspects related to this function. However, it does not provide any information about the importance of lactic acid bacteria in fermentation processes, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: While lakes and other potentially habitable surface environments may have existed early in Mars' history, during the Noachian era these climate-driven habitable environments would likely not be long-lived. Thus, any inhabiting life-forms would require refugia (see 7. 1. 5 in the supplementary material) to survive after transient, reducing greenhouse events had passed. Study of the martian climate has suggested a dramatic loss of atmospheric gases over time, but the causes of this loss are not well understood (Jakosky, 2021). Loss of an atmosphere impacts habitability at the surface because the stability of liquids like water is reduced there. The main proposed mechanisms that may account for atmospheric loss on Mars are solar wind stripping due to lack of a protective magnetic field and impact erosion. These mechanisms are discussed in more detail in the supplementary material. Some researchers have hypothesized that Mars may have had an ocean-sized body of water in its low-lying northern hemisphere (e. g. , Citron et al. , 2018), but this theory has substantial challenges. Most terrain north of 30°N on Mars is part of the northern lowlands, which is ∼1–3 km lower in elevation than the more ancient southern highlands. Some have interpreted shoreline features to exist along the rim of this basin. Near this area, there is strong evidence for inland-sea-sized bodies of water on Mars (105 to 107 km3 water, between the volumes of Earth's and double the Mediterranean Sea), including the Eridania sea and seas within Valles Marineris. There is some evidence for submarine hydrothermal activity in the geologic record of Eridania basin, similar to subseafloor hydrothermal processes that supply energy for chemotrophic communities in Earth's oceans. Water drained into the northern lowlands of Mars from an inland sea in the Eridania basin in the late Noachian and from seas in in the late Hesperian or early Amazonian. Water from both of these drainage events would have pooled in the northern lowlands, and some researchers have proposed that a long-lived northern ocean existed in this topographic low. However, geologic interpretations for the existence of this northern ocean are contested (e. g. , Salvatore and Christensen, 2014; Grant and Wilson, 2017), and the hypothesis of a long-lived northern ocean on Mars remains a matter of some debate. 7. 2. 1. 2. [SEP] Justify:

Output: The text corroborates the claim by discussing the potential for life on Mars, specifically mentioning potential habitable environments and the evidence of water on Mars which could sustain life. The exploration of Mars' conditions, including the presence and stability of water, directly relates to astrobiology's focus on understanding life beyond Earth. The mention of subsurface hydrothermal activity serving as a potential energy source for life further underlines the relevance of astrobiology to this text.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: Only a few examples of the systems used are shown even visually, leaving the reader unable to study more interesting cases in depth without re-doing the work themselves. The authors acknowledged that several recent studies exist in this space. They point out two advancements made in their work, worthy of further review. Similarly, it's important to evaluate the novelty of this work's claims vs previously available results, and the diversity of information made available to the reader. "First, we use structural models generated without any use of known structures of the target protein. For machine learning methods, this requires ensuring that no structure of the target protein was used to train the method. " This is done by limiting the scope of the work to GPCRs whose structures became available only after the training date of AlphaFold (April 30, 2018), as well as not using templates available after that date during prediction. The use of a time limit seems less preferable than the approach taken in Ref. 1 of discarding templates above a sequence identity cutoff. On the other hand, the 'ablation test' performed in Ref. 2 showed no loss in accuracy when no templates were used at all. Authors should discuss in more detail whether these modeling choices could change anything in their conclusions and why they made their choices compared to those in previous work. "Second, we perform a systematic comparison that takes into account the variation between experimentally determined structures of the same protein when bound to different ligands. " Cross-docking is indeed a more appropriate comparison than self-docking (as done in previous works), and the observation that the accuracy of AF models is similar to that between different holo structures of the same protein is interesting. Previous literature on cross-docking should however be discussed, and the well-known conclusions from it that small variations in side-chain positions, in otherwise highly similar structures, can lead to large changes in docked poses. It is important to realize that AlphaFold models are 'just another structure' - if previous literature is sufficient to show the sensitivity of rigid docking, doing it again on AF structures does not add to our understanding. Further, Ref. 3 might have already addressed the question of correlation between binding site RMSD and docking pose prediction accuracy - see e. g. 3 there (also Figure S15 in Ref. 2). [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations and nuances of structural models and machine learning methods in predicting protein behavior. It emphasizes that AlphaFold models and previous approaches have variability and sensitivity that may not lead to accurate predictions of real-world outcomes. For instance, it highlights that previous literature has demonstrated that small variations can lead to significant changes in results, suggesting that models may not accurately encompass real-world dynamics.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: The effects on ORP occurred in the absence of changes in growth rates, cell yields, and medium pH (Figure 3—figure supplement 1A-D). The ΔmVmax was reached during mid-exponential phase (approximately 5 hr) (Figure 3—figure supplement 1B), and at that time, wild-type L. plantarum cells but not the Δndh2 or ΔpplA strains were active in the ferrihydrite reduction assay (Figure 3—figure supplement 1E). This difference in ferrihydrite reduction activity similarly persisted in stationary phase cells (12 hr) (Figure 3—figure supplement 1F). These observations show that ndh2 and pplA contribute to the capacity of L. plantarum to reduce iron and have relevance to the ORP-dependent activities occurring during food fermentations (van Dijk et al. , 2000). Figure 3 with 2 supplements see all Download asset Open asset L. plantarum requires ndh2 and conditionally pplA for EET. (A) Reduction of Fe3+ (ferrihydrite) to Fe2+ with wild-type L. plantarum or EET deletion mutants in the presence of 20 μg/mL DHNA and 55 mM mannitol after growth in mMRS supplemented with 20 μg/mL DHNA and 1. 25 mM ferric ammonium citrate. Significant differences determined by one-way ANOVA with Dunnett’s post-hoc test, **** p < 0. 0001. (B) Redox potential of mMRS supplemented with 20 μg/mL DHNA and 1. 25 mM ferric ammonium citrate after inoculation with wild-type L. plantarum or EET deletion mutants. Significant ORP differences between the wild-type and mutant strains determined by two-way with Tukey’s post-hoc test, * p < 0. 05 (WT vs. Δndh2); # p < 0. 05 (WT vs. ΔpplA). (C) Current density generated by wild-type L. plantarum and deletion mutants in mCDM supplemented with 20 μg/mL DHNA. The avg ± stdev is shown. (D) Current density generated by L. plantarum and two L. lactis strains lacking pplA in mCDM. For L. [SEP] Justify:

Output: The text does not directly address the importance of lactic acid bacteria in fermentation processes. Instead, it focuses on specific activities related to wild-type L. plantarum and its deletion mutants regarding redox potential and ferrihydrite reduction, which suggests some role in fermentation without confirming the overall importance of lactic acid bacteria. Therefore, it is deemed irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: Past transient habitable environmentsA variety of martian environments have been studied for their potential to have been habitable in the past. Top among these environments are transient impact-generated hydrothermal systems, long-lived volcanically driven hydrothermal systems, and lakes that have been temporarily stable at the surface. Discussion of these environments is expanded in the supplementary material. 7. 2. 1. 3. Proposed habitable environments for modern MarsThe current state of knowledge regarding possible habitable environments for extant life on Mars is summarized in Carrier et al. (2020) and 6. 2. 1. 1). As the surface of Mars continued to get colder, the cryosphere would extend deeper, and potentially habitable subsurface environments would retreat to greater depths (Grimm et al. , 2017). Thus, the subsurface of Mars could have remained consistently habitable throughout its history and may continue to host microbial life today (Michalski et al. , 2013; Tarnas et al. , 2018). Surface features known as recurring slope lineae (RSL; Fig. 7. 3) observed by the Orbiter were initially thought to present potentially habitable environments on Mars (McEwen et al. , 2011). RSL are downward-moving darkened areas of hillsides coincident and recurrent with increased temperatures. However, the presence of liquid water in RSL is contested, and evidence suggests that RSL can be explained without the presence of liquid water (Dundas et al. , 2017; Schmidt et al. , 2017). RSL remain under “special region” status in NASA's planetary protection policies due to their potential habitability (see 10. 3. 1). FIG. 7. 3. Recurring slope lineae (RSL) on the surface of Mars. North is roughly to the left in this image, and the Sun is shining from the bottom. More details regarding this HiRISE image are available at Credit: NASA/JPL/University of Arizona. Ultimately, Earth-like organisms would require drastic adaptation to survive in surface environments on Mars, or in near-surface ice, brine, hydrated salt, or cave environments connected to Mars' desiccating and low-pressure atmosphere (Carrier et al. , 2020). The deep subsurface of Mars has potential for hosting Earth-like organisms, but only where groundwater is present. [SEP] Justify:

Output: The text corroborates the claim by discussing various environments on Mars that may have been habitable in the past and could potentially support microbial life today. It highlights research on transient hydrothermal systems and subsurface environments that might host life, which aligns with the central focus of astrobiology on the possibility of life beyond Earth.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: Further, the authors should discuss the commonly brought up problem of AlphaFold generating 'more apo-like structures' - are the models used here actually 'holo-like' because of the low RMSDs? (what RMSD differences are to be expected between apo and holo structures of these systems? ) How are the volumes of the pockets affected? The position on this problem taken by previous works is worth mentioning - "much higher rmsd values are found when using the AF2 models (. . . ), which reflect the difficulties in performing docking into apo-like structures" in Ref. 1 and "computational model structures were predicted without consideration of binding ligands and resulted in apo structures" in Ref. 2. Because of this 'apo problem', Ref. 2 assumed that rigid docking (as done here) would not succeed and used flexible docking where "two sidechains at the binding site were set to be flexible". In fact, the reader of this new paper will be left to wonder if it is not simply presenting a subset of the results already seen in Ref. 2, where "the success ratios dropped significantly for them because misoriented sidechains prevented a ligand from docking (Figure S14)". While this conclusion is not made as clear in Ref. 2 as it is here, a comparison of Figures 4 and S14 there will lead the reader to the same conclusion, and more -- that flexible docking meaningfully improves the performance of AF models, and more so than homology models. Finally, certain data analyses present in previous works but not here should be necessary to make this work more informative to the readers: a) Consideration of multiple top poses, e. g. , in Ref. 2, Figures 4 and S14 mentioned before, comparison of success rates in top 1 and top 3 docked poses add much context. b) Notes on the structural features preventing successful docking, see e. g. , in Ref. 1, Table 2 or in Ref. 4, Tables 2 and 4. This work has the potential to become an important piece of the puzzle, if deeper insights into the reasons for AF model failures are drawn by the authors. These could include a discussion of the problematic structural elements (clashes of side chain with ligands, missing interactions/waters, etc. ), potential solutions with some preliminary data (flexible docking, softening interactions, etc. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of certain computational models, specifically referencing the difficulties faced by AlphaFold models in accurately predicting behavior related to docking into apo-like structures. It highlights that previous works found 'much higher rmsd values' when using these models, indicating that they do not always accurately reflect real-world scenarios. This suggests that not all economic or computational models yield accurate predictions, thereby challenging the claim.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: plantarum, the mCDM was supplemented with 20 μg/mL DHNA. The data correspond to the average of two (D) or three (A to C) biological replicates per strain. See also Figure 3—figure supplement 1 and Figure 3—figure supplement 2 and related data in Figure 3—source data 1. Figure 3—source data 1 Raw data of Figure 3A–C. Download elife-70684-fig3-data1-v2. xlsx Use of an anode as an external electron acceptor instead of ferrihydrite showed a similar, but not identical genetic dependency. L. plantarum Δndh2 produced a significantly lower current density (Figure 3C) and a lower peak current (Figure 3—figure supplement 2A). Surprisingly, L. plantarum ΔpplA was able to produce the same amount of current as the wild-type strain, suggesting that the lipoprotein PplA is not essential and might not be involved in anode reduction through EET. This observation led us to investigate the anodic-EET ability of other LAB species lacking pplA like Lactococcus lactis (Figure 3D). DHNA was not provided to these strains because they can synthesize demethylmenaquinone and other quinones (Rezaïki et al. , 2008). Both L. lactis strain IL1403 and strain KF147 were capable of current generation, confirming that PplA is not essential for LAB to produce current. This is consistent with the finding that other extracellular reductases besides PplA are responsible for EET activity in Gram-positive bacteria (Light et al. , 2019). Taken together these results show that EET activity is dependent upon the presence of the putative FLEET locus, and specifically ndh2 and conditionally pplA. L. plantarum increases energy conservation and balances intracellular redox state when performing EET Building from studies in E. faecalis (Keogh et al. , 2018), it has been suggested that EET improves growth by either enabling iron to be acquired as a macronutrient or by enhancing respiration (Jeuken et al. , 2020). It is worth noting that several studies have shown that L. plantarum does not require iron to grow (Elli et al. [SEP] Justify:

Output: The text does not address the claim directly or provide relevant information about the importance of lactic acid bacteria in fermentation. Instead, it discusses specific genetic and functional aspects of the Lactobacillus plantarum strain in relation to current generation and electron transfer activity, which is a narrower topic and does not provide insight into their role in fermentation processes.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: Such a scenario would make venusian origins of life more difficult, although a cloud-based origin of life is conceivable (e. g. , Dobson et al. , 2000). If the atmosphere of Venus never cooled enough to condense water on its surface, it would likely have lost much of its primordial water rapidly, within 100 million years (Hamano et al. , 2013). cooled enough to condense liquid water on its surface, it is possible that life could have emerged under conditions similar to origins on Earth. Life exhibits an ability to adapt and expand to fill even extreme habitats (see 6. 3). Furthermore, a “faint young Sun” (4. 1. 4) likely resulted in lower equilibrium temperatures on the surface of early Venus. General circulation models incorporating atmospheric feedback show that if Venus has been rotating slowly (taking longer than 16 Earth days per revolution) for most of its history, its surface may have remained hospitable until as recently as 0. 715 Ga (Way et al. , 2016). Venus may have experienced chemical weathering and subsequent carbon burial that provided a negative climate feedback as the young Sun warmed, helping to maintain a habitable environment on the surface of Venus over geologic timescales (Zolotov, 2019). If the surface environment at Venus gradually warmed to evaporate an Earth-sized ocean of water, organisms in that ocean may have had time to adapt to changing conditions and inhabit the clouds (e. g. , Limaye et al. , 2018), although such a scenario faces significant challenges. Greaves et al. (2021) identified an absorption feature in observations of Venus that they attributed to phosphine (PH3) in the cloud deck, which they claimed as a potential biosignature. However, this interpretation is contested. See 8. 3. 1. 3 for more on the possibility of phosphine on Venus. The crust of Venus exhibits widespread consistency in its surface age, ranging from 0. 3 to 0. 7 Ga, as inferred from crater densities (Solomon et al. , 1999). The broad consistency of surface age implies that a major catastrophe triggered a global resurfacing event (Strom et al. , 1994). Possible explanations for such an event are described in the supplementary material. [SEP] Justify:

Output: The text corroborates the claim by discussing the potential for life on Venus, illustrating how conditions may have allowed for the emergence of life similar to origins on Earth. The text explores various scenarios of habitability on Venus, such as the possibility of life adapting to extreme habitats, which is central to the study of astrobiology.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: ), or proposals for metrics better than RMSD to score the soundness of pockets generated by AF for docking. 1. Díaz-Rovira, A. M. , Martín, H. , Beuming, T. , Díaz, L. , Guallar, V. , & Ray, S. S. (2023). for Virtual Screening? Application of to AlphaFold2 Predicted Structures. Journal of and Modeling, 63(6), 1668-1674. 2. Heo, L. , & Feig, M. (2022). Multi-state modeling of G-protein coupled receptors at experimental accuracy. Proteins: Structure, Function, and Bioinformatics, 90(11), 1873-1885. 3. Beuming, T. , & Sherman, W. (2012). Current assessment of docking into GPCR crystal structures and homology models: Successes, challenges, and guidelines. Journal of and Modeling, 52(12), 3263-3277. 4. Scardino, V. , Di Filippo, J. I. , & Cavasotto, C. (2022). How good are AlphaFold models for docking-based virtual screening? [Preprint]. Chemistry. Author response We thank the reviewers and editor for their careful evaluation of our manuscript, and we appreciate their favorable assessment of our work. Below, we clarify a few points concerning the relationship between our study and previous studies evaluating ligand docking to protein models. As reviewer 2 correctly notes, several previous assessments of AF2 models have simply excluded templates above a sequence identity cutoff when using AF2 to predict structures. Such AF2 predictions are still informed by all structures in the PDB before April 30, 2018, because these structures were used to train AF2—that is, to determine the tens of millions of parameters (“weights”) in the AF2 neural network. Machine learning methods nearly always perform better when evaluated on the data used to train them than when evaluated on other data. For this reason, we consider AF2 models only for proteins whose structures were not used to train AF2—that is, for proteins whose structures were not available in the PDB before April 30, 2018. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of models like AlphaFold2 (AF2) that are trained using specific datasets. It notes that machine learning methods, including AF2, typically perform better on training data compared to unseen data, implying that models may not accurately predict real-world behavior when evaluated under different conditions. This suggests that economic models, in general, may face similar challenges regarding accuracy in real-world predictions.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: , 2000; Weinberg, 1997). To test whether EET allowed increased iron acquisition by L. plantarum, we measured intracellular iron by Plasma-(ICP-MS). There was no significant difference in intracellular iron concentrations between L. plantarum growth in mMRS supplemented with DHNA and iron compared to growth in mMRS alone (Figure 4—figure supplement 1). Moreover, deletion of ndh2 did not significantly change the amount of intracellular iron (Figure 4—figure supplement 1). ICP-MS showed that other redox-active metals used for EET, such as manganese and copper (Kouzuma et al. , 2012; Fan et al. , 2018) were also not affected (Figure 4—figure supplements 1 and 2). In contrast to studies in E. faecalis in which iron supplementation leads to intracellular accumulation of this metal (Keogh et al. , 2018), these data show that L. plantarum does not use EET to increase its acquisition of iron or other redox-active metals, suggesting EET may instead play a role in energy conservation. We next sought to understand if EET impacts energy conservation in L. plantarum by comparing its growth and ATP levels in the presence of a polarized anode. The highest current density (i. e. greatest EET activity) produced by L. plantarum in mannitol CDM typically occurred within 24 hr after inoculation into the bioreactor (Figure 1C). At this point, there was an approximately 4-fold higher dry cell weight and 2-fold higher numbers of viable cells compared to L. plantarum incubated in open circuit (OC) conditions (Figure 4A–B) Current density declined from its maximum value when L. plantarum cells performing EET were in exponential growth (Figures 1C and 4C). By comparison, growth was not observed until two days later under OC conditions (Figure 4C). During peak current production, intracellular ATP levels were significantly higher (4. 5-fold) under EET compared to OC conditions (Figure 4D and Table 1). These results strongly suggest faster ATP accumulation under EET conditions allowed L. plantarum to exit lag phase more rapidly. ATP levels were also greater in L. [SEP] Justify:

Output: The text does not mention lactic acid bacteria as being important for fermentation processes. Instead, it discusses experiments involving L. plantarum and its interaction with iron acquisition and energy conservation mechanisms. While L. plantarum is a type of lactic acid bacteria, the focus of the text is on its iron acquisition and ATP levels rather than its overall importance in fermentation.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: At present, it is difficult to reconcile any scenario for the evolution of Venus as a planet that may still be habitable for even the most extreme and adaptive of Earth-like life. Still, Venus presents an excellent laboratory for better understanding atmospheric evolution and surface–atmosphere interactions under more extreme conditions than those on Earth. was ever habitable, similar processes could be operating on exoplanets under similar conditions, and studying Earth's nearest neighbor can provide insights into the habitability of such exoplanets. See 9. 3. 1. 3 for considerations regarding life as we don't know it on Venus. 7. 2. 3. EuropaJupiter's moon Europa (Fig. 7. 5) is an especially attractive target in the study of habitability. Evidence supports the presence of an ocean over 100 km deep with an overlying ice shell over 20 km thick. The large orbital eccentricity of Europa, maintained by orbital resonances with Io and Ganymede, causes extensive tidal heating that helps maintain a liquid ocean (Tobie et al. , 2003). Silicate rock in contact with the europan ocean is likely to provide a source of chemical energy for life. Chemical reactions and leaching interactions between Europa's ocean and mantle may have altered the composition and oxidation state of the ocean, which have important consequences for habitability and possible origins of life. FIG. 7. 5. The surface of Europa, as imaged by the Galileo spacecraft. Cycloid ridges and chaos terrains imply recent geologic activity that helps us understand the potential habitability of this intriguing world. Credit: NASA/JPL-Caltech/SETI Institute. 7. 2. 3. 1. Evidence for an oceanThe strongest evidence for a subsurface europan ocean comes from magnetic sounding (Khurana et al. , 2009), with additional support provided by geological features (e. g. , Figueredo and Greeley, 2004). Jupiter applies an oscillating magnetic field to Europa. An induced magnetic field that oscillates along with Jupiter's rotation has been observed from Galileo magnetometer measurements near Europa (Kivelson et al. , 2000), and the best explanation of these measurements is a liquid water ocean with a salinity roughly comparable to oceans on Earth (Hand and Chyba, 2007). Other materials cannot explain the induced field observed near Europa. A more detailed discussion is found in the supplementary material. 7. 2. 3. 2. [SEP] Justify:

Output: The text corroborates the claim by discussing various celestial bodies such as Venus and Europa, which are of interest for astrobiological studies. It highlights that studying these planets can provide insights into the habitability of exoplanets, indicating that astrobiology looks to understand potential for life beyond Earth. Specifically, it mentions 'evidence supports the presence of an ocean' on Europa, emphasizing the search for life in environments that may resemble those that could support life beyond our planet.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: , 2023; Heo and Feig, 2022; Lee et al. , 2022; Lee et al. , 2023; Liang et al. , 2022; Qiao et al. , 2022; Scardino et al. , 2023; Wong et al. , 2022). Our study stands apart in two regards. First, we use structural models generated without any use of known structures of the target protein. For machine-learning methods, this requires ensuring that no structure of the target protein was used to train the method. Second, we perform a systematic comparison that takes into account the variation between experimentally determined structures of the same protein when bound to different ligands. Our results reveal both strengths and weaknesses of AF2 models. The structural accuracy of ligand-binding pockets in AF2 models is usually substantially higher than that of traditional homology models. Indeed, the typical difference between corresponding binding pockets in an AF2 model and in an experimentally determined structure is only slightly larger than the typical difference between two experimentally determined structures of the same protein with different ligands bound. Surprisingly, however, ligand-binding poses predicted given AF2 models are not significantly more accurate than those predicted given traditional models and are much less accurate than those predicted by docking computationally to experimentally determined protein structures. Our results provide guidelines as to how AF2 models should—and should not—be used for effective ligand-binding prediction. Our findings also suggest opportunities for improving structure prediction methods to maximize their impact on drug discovery. of proteins and models to ensure a fair comparison Evaluating the accuracy of predicted ligand-binding poses requires that we examine protein–ligand complexes whose structures have been determined experimentally. We wish to ensure, however, that the predicted structures of a given protein are not informed by experimentally determined structures of that same protein. AF2 and other recent neural-network-based protein structure prediction methods use experimentally determined protein structures in two ways: first, to train the neural network and second, as templates for prediction of individual protein structures (Baek et al. , 2021; Jumper et al. , 2021). The AF2 neural network was trained on structures in the Bank (PDB) (Berman et al. , 2000) as of April 30, 2018 so we evaluated structural models of proteins for which no experimentally determined structure was available as of that date. [SEP] Justify:

Output: The text contrasts the claim by discussing the limitations of AF2 models in predicting ligand-binding poses compared to traditional models, suggesting that not all models, including some that might be categorized under economic models, perform accurately in real-world scenarios. The text notes that 'ligand-binding poses predicted given AF2 models are not significantly more accurate than those predicted given traditional models,' indicating that some models fail to achieve reliable predictions, thereby refuting the notion that all economic models accurately predict behavior.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: plantarum when in the presence of both mannitol and DHNA, compared to either mannitol or DHNA separately (Figure 4D). Thus, EET allows L. plantarum to initiate growth and accumulate ATP more rapidly, indicating that EET significantly increases energy conservation in L. plantarum. Figure 4 with 3 supplements see all Download asset Open asset Growth, ATP, and redox balance of L. plantarum changes when an anode is provided as an extracellular electron acceptor. These measurements and the current density plot shown in Figure 1C are from the same experiment. (A) Viable cells and (B) dry weight at the point of maximum current density under current circulating conditions (EET) and at open circuit conditions (OC) at the same time point. (C) Change in cell numbers measured by OD600 over time in the bioreactors under EET (continuous line) and OC conditions (dotted lines). (D) ATP production per OD600 unit and (E) NAD+/NADH ratios at the point of maximum current density. The bioreactors were shaken vigorously to dislodge cells before sampling. The avg ± stdev of three biological replicates is shown. Significant differences were determined by one-way ANOVA with (A and B) Dunn-Sidak post-hoc test (n = 3) and (D and E) Dunnett’s post-hoc test (n = 3), * p < 0. 05; ** p < 0. 01; *** p < 0. 001; **** p < 0. 0001. See also Figure 1 panel C and Figure 4—figure supplement 3 and related data in Figure 4—source data 1. Figure 4—source data 1 Raw data of Figure 4A–D. Download elife-70684-fig4-data1-v2. xlsx Table 1 Bioenergetic balances suggest energy conservation under EET conditions occurs via substrate-level phosphorylation. The reactors contained 20 µg/mL of DHNA and mannitol as the electron donor. Balances were calculated with data obtained by day four from Figure 5. See also Supplementary file 1. SLP stands for substrate-level phosphorylation. Yfermentation refers to the total fermentation products obtained (see Supplementary file 1) per mol of sugar consumed. [SEP] Justify:

Output: The text does not provide any direct information or evidence relating to the importance of lactic acid bacteria in fermentation. Instead, it discusses the bioenergetic balances and growth conditions of L. plantarum under specific experimental setups, but does not imply its significance in fermentation processes. Therefore, it is deemed irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: Surface conditionsEuropa rests deep within the extensive magnetosphere of Jupiter. The strong jovian magnetic field traps charged p0. 01 nbar; Kliore et al. , 1997), so these p7. 5) is covered in tectonic features reminiscent of subduction faults and fractures common on Earth (Leonard et al. , 2018). There is some evidence of subduction (Kattenhorn and Prockter, 2014), although features may be created by interaction between the conductive and convective ice layers, mediated by tidal forces (Barr and Hammond, 2015). Some evidence suggests that plumes may be erupting from the surface of Europa. Observations with the Telescope (Roth et al. , 2014b) and in situ measurements from Galileo (Jia et al. , 2018; Arnold et al. , 2019) each show some indications of water vapor lofted to high altitudes. Later observations with Hubble have seen no further evidence of plumes, suggesting that europan plumes can only be intermittent, if they are indeed present (Roth et al. , 2014a). Further studies have had difficulty corroborating these observations—there does not appear to be any thermal anomalies on the surface that would be expected where the plumes erupt (Rathbun and Spencer, 2020), a stark contrast with the plumes of Enceladus (Porco et al. , 2014). does have plumes, they are likely to contain material not from the ocean but from shallower melt or brine pockets within the ice shell, as fractures are unlikely to reach directly from the ocean to the surface (Rudolph and Manga, 2009; Howell and Pappalardo, 2019). 7. 2. 3. 3. Ocean habitabilityEuropa seems to have many of the conditions required to support habitable environments. Hydrothermal vents likely exist in the subsurface ocean of Europa, providing a possible energy source for metabolism (Lowell and DuBose, 2005; Vance and Melwani Daswani, 2020). If there is a transport mechanism through the ice shell (e. g. , Kalousová et al. , 2014), introduction of oxidized surface materials may provide rich sources of chemical energy for the likely reduced ocean (Fig. 7. 6; Vance et al. , 2019; Hand et al. , 2020). [SEP] Justify:

Output: The text corroborates the claim by discussing the conditions on Europa, which suggest the potential for habitable environments in its subsurface ocean. Phrases like 'many of the conditions required to support habitable environments' and references to 'hydrothermal vents' indicate that astrobiological research is concerned with the possibilities of life beyond Earth, particularly within our solar system.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: , 2021), we find that the global structural accuracy of the AF2 models is substantially better than that of the traditional template-based models. In particular, when computing RMSDs based on all non-hydrogen atoms in each protein, we find a median RMSD of 2. 9 Å between AF2 models and corresponding experimentally determined structures, compared to a median RMSD of 4. 3 Å for traditional models (Figure 1—figure supplement 1). Next, we turn our attention to the orthosteric binding pocket of each protein—that is, the region where native ligands and most other ligands, including those in our dataset, bind. AF2 was trained to optimize global structural accuracy, with an emphasis on correctly predicting the structure of the protein backbone. The accuracy of binding pocket prediction, on the other hand depends heavily on side-chain conformations in this local region. Nevertheless, we find that AF2 predictions of binding pocket structures are typically very accurate. In fact, the binding pocket RMSD between an AF2 model and an experimentally determined structure is typically nearly as low as the RMSD between two experimentally determined structures of the same protein with different ligands bound (Figure 1). In contrast, binding pockets in the traditional template-based models are much less accurate, with a median RMSD of 3. 3 Å for traditional models vs. 1. 3 Å for AF2 models. We note that the binding pockets of a few AF2 models are highly inaccurate (approximately 5 Å RMSD), as is the case for several of the traditional models. Figure 1 with 2 supplements see all Download asset Open asset Structural accuracy of modeled binding pockets. Binding pockets are defined to include all amino acid residues with any atom within 5 Å of the ligand in an experimentally determined structure. We compute all-atom binding pocket root mean squared deviations (RMSDs) between each modeled structure and all experimentally determined structures of the same protein. For comparison, we also compute binding pocket RMSDs between all pairs of experimentally determined structures of the same protein with different ligands bound. The middle line of each box in the plot is the median RMSD, with the box extending from the first to the third quartile and defining the ‘interquartile range’. [SEP] Justify:

Output: The text contrasts the claim by discussing the performance of AF2 models compared to traditional template-based models in predicting protein structures. While it highlights the superior accuracy of AF2 models, it also acknowledges inaccuracy in some predictions, stating 'we note that the binding pockets of a few AF2 models are highly inaccurate.' This implies that not all models, including economic ones, maintain accuracy in predicting outcomes, undercutting the claim that all economic models accurately predict real-world behavior.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: Ymannitol is the ATP produced from the total fermentation products per mol of sugar consumed, and YATP is the dry weight measured per mol of ATP produced from fermentation products. NADH consumed*Calculated ATP†(from metabolites)Biomass yield-dw/mol-mannitolmmol product/mmol-mannitolmol ATP/mol mannitolg dw/mol 6. 44 ± 0. 48 via anode16. 69 ± 2. 72 via SLP16. 6 ± 1. 54. 85 ± 0. 331. 53 ± 0. 131. 59 ± 0. 133. 09 ± 0. 36OC5. 51 ± 0. 97 via SLP5. 7 ± 0. 67. 21 ± 1. 410. 87 ± 0. 090. 89 ± 0. 098. 06 ± 0. 86 * Calculated based on production of 3 mol of NADH produced per mol of mannitol, 1 mol of NAD+ per lactate, 2 mol of NAD+ per ethanol, 2 mol of NAD+ mol per succinate produced and 0. 5 mmol of NAD+ per mol of electrons harvested on the anode. † Calculated based on production of 1 mol of ATP per lactate, 2 mol per acetate, 1 mol per ethanol, and 3 mol per succinate produced. Because fermentation, anaerobic respiration, and aerobic respiration are each associated with a different NAD+/NADH ratio, energy conservation is linked to intracellular redox homeostasis (Holm et al. , 2010). Therefore, we probed redox homeostasis in L. plantarum under EET conditions by measuring intracellular NAD+/NADH at the point of maximum current density (Figure 4E). L. plantarum showed an 8-fold higher NAD+/NADH ratio under EET conditions compared to OC (Figure 4E). This result was not limited to the presence of a polarized anode as L. plantarum also contained a significantly higher NAD+/NADH ratio when Fe3+ was available as a terminal electron acceptor (Figure 4—figure supplement 3). These NAD+/NADH ratios are more similar to those found for in E. coli performing aerobic respiration (de Graef et al. , 1999) or G. [SEP] Justify:

Output: The text does not directly address the importance of lactic acid bacteria in fermentation processes. Instead, it discusses ATP production, redox homeostasis, and NAD+/NADH ratios in Lactobacillus plantarum under different conditions, which may imply fermentation activities but does not explicitly confirm or deny the significance of lactic acid bacteria in the fermentation process.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: Pockets of concentrated brine may also become trapped in the ice shell, thereby providing environments suitable for psychrophilic (6. 3. 1. 1) and halophilic (6. 3. 3. 1) organisms (Boetius et al. , 2015; Cooper et al. , 2019). Considerations for life as we don't know it on Europa are discussed in 9. 3. 2. 2. FIG. 7. 6. Sources of biologically important molecules that could potentially sustain life in Europa's ocean. The high-radiation environment at the surface acts as a source of oxidants, and water–rock reactions at the seafloor may act as a source of reductants. If there is some process that cycles crustal material between the surface and the ice–ocean interface, similar to plate tectonics on Earth, this interface likely represents a habitable environment. Europa's ice shell is expected to be quite thick (over 20 km), which may preclude such cycling. Subduction on Europa likely cannot cycle surface material directly into the ocean (Howell and Pappalardo, 2019). This has important consequences for studies of the habitability of the europan ocean that rely on transport of oxidants from the surface into the ocean (e. g. , Hand et al. , 2009; Vance et al. , 2016). There is mounting evidence that the europan ice shell is in the process of thickening and cooling (Leonard et al. , 2018; and McNamara, 2019; Howell and Pappalardo, 2019). The thickness and properties of the ice shell also dictate how energy from tidal interactions will be distributed (Matsuyama et al. , 2018), so a thorough understanding of the dynamics of the europan ice shell is critical to understanding the habitability of the ocean. The location of Europa in the and its bulk density suggest that it is likely constructed of rock, ice, and metals sourced from CI chondrite material (Sohl et al. , 2002), although there may be an additional cometary component (Néri et al. , 2020). Laboratory analog research on leaching of salts from chondritic material suggests MgSO4 may be a primary salt in the europan ocean (Kargel et al. , 2000). This is supported by putative detection of MgSO4 spectral features on the surface (McCord et al. [SEP] Justify:

Output: The text corroborates the claim by discussing the potential for life in the subsurface ocean of Europa, highlighting environments that could be suitable for different organisms. It elaborates on factors such as the presence of concentrated brine, biologically important molecules, and the dynamics of the ice shell, all of which contribute to understanding habitability beyond Earth. This directly relates to the field of astrobiology, which investigates the conditions and potential for life in extraterrestrial environments.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: Whiskers extend to last data points that are within 150% of the interquartile range, and outlier data points beyond those are shown individually. The plotted data is based on 150 RMSD values (comparisons) for experimentally determined structures with different ligands bound, 52 for AlphaFold 2 models, and 78 for traditional models. Binding pose prediction using AF2 models or traditional models yields similar accuracy Next, we assess the accuracy of ligand-binding poses predicted by computational docking to AF2 models and traditional template-based models. For each ligand we consider, the binding pose to a target protein is known based on an experimentally determined structure of the ligand bound to the protein, which we call the reference structure. Using industry-standard software, we docked each ligand to both AF2 and GPCRdb models of the protein. A predicted pose is considered correct if its RMSD from the experimentally determined pose is ≤2. 0 Å (Figure 2), a widely used criterion for correct pose prediction (Erickson et al. , 2004; Gohlke et al. , 2000; Paggi et al. , 2021). Figure 2 with 2 supplements see all Download asset Open asset Accuracy of ligand-binding poses predicted by computational docking to AlphaFold 2 models, traditional template-based models, or protein structures determined experimentally in complex with a ligand different from the one being docked. We plot the fraction of docked ligands whose pose is predicted correctly (see Methods). Error bars are 90% confidence intervals calculated via bootstrapping. *** for p-values <0. 001, ns for p-values >0. 05. 40 - 54 ligands were evaluated for each set of structures or models. For comparison, we also dock each ligand to structures of the same protein determined experimentally with other ligands bound (cross-docking). Note that when calculating pose prediction accuracy (Figure 2), we exclude cases where the ligand is docked back to the reference structure; such ‘self-docking’ yields much higher accuracy (Figure 2—figure supplement 1) but is of little practical utility, because in practice one wishes to predict binding poses that have not already been determined experimentally. [SEP] Justify:

Output: The text contrasts the claim by discussing the accuracy of ligand-binding poses predicted by computational models (AlphaFold 2 and traditional models) rather than economic models. It emphasizes that predicted poses using these models show accuracy based on experimental structures. This suggests that while some computational models can be accurate, it does not imply that all models in different fields, such as economics, can predict behavior accurately.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: sulfurreducens performing anaerobic respiration than in LAB performing fermentation (Guo et al. , 2017). Taken together, our data indicate that EET is involved in energy conservation, and the intracellular redox balance during EET mimics a respiratory rather than a fermentative process. EET increases fermentative metabolism through substrate-level phosphorylation and reduction in extracellular pH Metal-reducing bacteria use EET in anaerobic respiration (Richter et al. , 2012; Shi et al. , 2007). Ndh2 is considered an anaerobic respiratory protein, and L. plantarum can perform anaerobic respiration with exogenous menaquinone and heme using an electron transport chain (Brooijmans et al. , 2009b). This led us to hypothesize that those electron transport proteins could also be involved for EET to conserve energy as part of anaerobic respiration. To test this hypothesis, we examined whether any of the known electron transfer proteins needed for PMF generation in aerobic and anaerobic respiration are required for L. plantarum EET. Neither the addition of heme to restore bd-type cytochrome (cydABCD) used in aerobic respiration, nor deletion of the respiratory nitrate reductase (ΔnarGHJI) significantly altered current production (Figure 5—figure supplement 1A-B). Because Ndh2 is a type-dehydrogenase which does not contribute to a proton gradient (Lin et al. , 2008; Nakatani et al. , 2020), these observations show that while EET does involve a respiratory protein, it does not involve any of the known PMF-generating electron transfer proteins in L. plantarum. Respiration is also associated with the tricarboxylic acid (TCA) cycle. L. plantarum, like other LAB, does not possess an oxidative branch of the TCA cycle and only contains a reductive branch (Tsuji et al. , 2013). To probe whether the reductive branch was active during EET, we also examined production of succinate, the terminal end-product of the reductive branch. EET did not increase the succinate concentration (Figure 5—figure supplement 2). [SEP] Justify:

Output: The text discusses various aspects of anaerobic respiration and electron transfer processes involving L. plantarum, a lactic acid bacterium (LAB). However, it primarily focuses on respiration rather than fermentation. While it mentions LAB, it does not provide direct evidence supporting the claim about their importance in fermentation processes, therefore rendering it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: , 1998; Fox-Powell et al. , 2019), although other materials may explain the observed spectra (Hibbitts et al. , 2019), such as NaCl that may come from the subsurface (Trumbo et al. , 2019). Some studies (e. g. , Brown and Hand, 2013) suggest that surface S and O may be implanted exogenously from volcanic activity on Io, and their presence on the surface does not preclude an ocean dominated by chlorides such as NaCl. 7. 2. 3. 4. Upcoming explorationAn overview of the upcoming and JUICE missions is included in the supplementary material. 7. 2. 4. EnceladusEnceladus is a small (504 km diameter), icy moon of Saturn. Despite its small size, Enceladus has received abundant scientific attention, including measurements from the and Cassini missions. This moon is of particular astrobiological interest, as there is strong evidence of a global ocean below its icy surface that is in contact with a rocky core. The existence of a subsurface ocean on Enceladus is supported by several lines of evidence. Images taken by Cassini show a physical libration (wobble) of the icy crust that is too large for an icy shell anchored to the silicate core of the moon but is consistent with a subsurface liquid ocean (Thomas et al. , 2016). Gravity and shape data of the moon indicate the icy crust may be tens of kilometers thick on average but less than 11 km thick at the southern pole, with a liquid ocean beneath (Beuthe et al. , 2016; Čadek et al. , 2016). Numerous persistent jets of water vapor and small icy p7. 7; e. g. , Porco et al. , 2006; Waite et al. , 2006; Postberg et al. , 2009, 2011). FIG. 7. 7. The south polar plumes of Enceladus, lit by the Sun from behind the camera of the Cassini spacecraft. Ice grains from subsurface reservoirs of liquid water are ejected into space and reflect the sunlight. Credit: NASA/JPL-Caltech/SSI. [SEP] Justify:

Output: The text supports the claim by discussing Enceladus, a moon of Saturn that is of particular astrobiological interest. It mentions evidence of a subsurface ocean that is likely in contact with rocky materials, which suggests potential conditions for life. The exploration of ocean worlds like Enceladus is a key focus in astrobiology, indicating that studies related to these celestial bodies are directly tied to the exploration of the potential for life beyond Earth.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: Strikingly, binding pose prediction accuracy was similar when using AF2 models or traditional template-based models, despite the fact that binding pocket structures were substantially more accurate in AF2 models. Although the fraction of ligands docked correctly was slightly higher when using AF2 models (15%) than when using traditional models (9%), this difference was not statistically significant (p > 0. 5). On the other hand, binding pose prediction accuracy was far higher when docking to experimentally determined protein structures (44%), even though these structures were determined in complex with ligands different from those being docked. The docked poses analyzed above were determined with the widely used commercial docking software package Glide, run in SP mode (for ‘standard precision’) (Friesner et al. , 2004). To verify the robustness of our results, we repeated all docking experiments using a completely different docking software package—Rosetta docking (Park et al. , 2021)—as well as with Glide run in XP mode (for ‘extra precision’) (Friesner et al. , 2006). In both cases, we again found that, when used for ligand-binding pose prediction, AF2 models substantially underperformed experimentally determined structures and did not significantly outperform traditional models (Figure 2—figure supplement 2). In fact, the difference in binding pose prediction accuracy between AF2 models and traditional models was even smaller when using Rosetta docking or Glide XP than when using Glide SP. Closer look at discrepancy between structural accuracy and pose prediction accuracy The results of the previous two sections contrast sharply with one another. AF2 models nearly match experimentally determined structures—and are much better than traditional template-based models—in binding pocket accuracy, as measured by a standard structural metric. Yet AF2 models fare much worse than experimentally determined structures—do not significantly outperform traditional models—when used to predict ligand-binding poses. Figures 3 and 4 provide illustrative examples. Figure 3 with 1 supplement see all Download asset Open asset An example in which docking to an AlphaFold 2 (AF2) model yields poor results even though the model’s binding pocket has high structural accuracy. [SEP] Justify:

Output: The text contrasts the claim by providing evidence that different models, specifically AF2 models and traditional template-based models, show varying degrees of accuracy in predictions. Despite AF2 models having high structural accuracy, they do not significantly outperform traditional models in terms of binding pose prediction accuracy. This suggests that not all models are equally reliable in predicting real-world behavior, directly opposing the claim that 'all economic models accurately predict real-world behavior.'


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: , 2018Rifampicin-resistant mutant of NCIMB8826Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)MLES100This studyDeletion mutant of NCIMB8826 lacking ndh2Plasmid information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)MLES101This studyDeletion mutant of NCIMB8826 lacking pplAPlasmid information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)MLEY100This studyDeletion mutant of NCIMB8826 lacking narGHIJPlasmid information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)B1. 3Yin et al. , 2018 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)AJJ11Yu et al. , 2021 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)8. 1Yu et al. , 2021 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)ATCC 202195Wright et al. , 2020 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus plantarum)NCIMB700965Heeney and Marco, 2019 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus pentosus)BGM48Golomb et al. , 2013 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus casei)BL23Mazé et al. , 2010 Strain information listed in Supplementary file 3Strain, strain background (Levilactobacillus brevis)ATCC 367Makarova et al. , 2006 Strain information listed in Supplementary file 3Strain, strain background (Lactococcus lactis)KF147Siezen et al. , 2010b Strain information listed in Supplementary file 3Strain, strain background (Lactococcus lactis)IL1403Bolotin et al. [SEP] Justify:

Output: The text provides detailed strain information for various Lactiplantibacillus plantarum and related strains but does not directly address the importance of lactic acid bacteria in fermentation processes. As such, it is irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: The composition of these plumes was sampled directly by the Cassini spacecraft with multiple plume fly-throughs, in addition to in situ samples and measurements of the E-ring of Saturn, which is sourced from the plumes of Enceladus (Spahn et al. , 2006). A variety of grains were observed in the plumes, with compositions ranging from salt-rich (Postberg et al. , 2009; Khawaja et al. , 2019) to water-dominated (Waite et al. , 2006; Teolis et al. , 2010), to grains rich in organic molecules or silicates (Postberg et al. , 2008, 2018). In addition to the grain composition, Cassini instruments measured the plume gas composition and found it to be predominantly H2O, along with significant CO2, CH4, NH3, and H2 (Waite et al. , 2006, 2017). These measurements indicate the icy plumes are likely sourced from a subsurface liquid ocean in contact with a silicate core. Alternative explanations for the source of the plumes, discussed in the supplementary material, have been considered, but none are consistent with observations. To remain consistent with observed salt and NH3 measurements, the temperature of the subsurface ocean may be above −1°C on average (Glein et al. , 2018). Similarly, from constraints of CO2 in the plume, NaCl and bicarbonate p7. 1. 1. 1 in the supplementary material). A source of chemical energy may be available in the form of H2 and CH4 generated from serpentinization of the silicate core and radiolysis of water in the seafloor pore space (Bouquet et al. , 2017). The combination of all these factors indicates that the enceladean ocean may be habitable to life as we know it. It is unknown if the conditions for the origin of life, either at present or in the past, have been met on Enceladus. Even if the conditions for life and abiogenesis are present in the enceladean ocean, the moon may be too young to have formed a biosphere. Models and measurements of saturnian moons and rings indicate they may be only a few hundred million years old or less (Ćuk et al. , 2016; Iess et al. , 2019), although this proposal is debated (Crida et al. [SEP] Justify:

Output: The text corroborates the claim by discussing the possibility of habitable conditions in the subsurface ocean of Enceladus, which is a key area of interest in astrobiology. It states that the enceladean ocean may be habitable to life as we know it and explores the composition of plumes that could indicate conditions favorable for life. Moreover, it highlights that while it's uncertain if the conditions for the origin of life were met, the exploration of such environments directly relates to the goals of astrobiology in understanding potential life beyond Earth.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: We predict the binding pose of the drug aprepitant to its target, the neurokinin-1 receptor (NK1R) given either the AF2 model (orange) of NK1R or the experimentally determined structure (blue, PDB entry 6E59) of NK1R bound to a different ligand, L760735. (A, B) The binding pocket of the AF2 model is more similar (lower root mean squared deviation [RMSD]) than the binding pocket of the L760735-bound structure to the binding pocket of the aprepitant-bound structure (the ‘reference structure’, white, PDB entry 6J20). Amino acid residues whose positions differ most from the reference structure are shown in sticks (see Methods). (C, D) The aprepitant binding pose predicted by docking is much less accurate (higher RMSD) when using the AF2 model than when using the L760735-bound structure. Ligand L76035 shares a scaffold with aprepitant; for completeness, we include another example with highly dissimilar ligands in Figure 3—figure supplement 1. We note that the experimentally determined L760735-bound structure is a low-resolution structure with suboptimal goodness of fit to experimental data; despite this, docking aprepipant to this structure yields an accurate pose. Figure 4 Download asset Open asset An example in which docking to a traditional template-based model yields better results than docking to an AlphaFold 2 (AF2) model, even though the AF2 model’s binding pocket has higher structural accuracy. We predict the binding pose of the psychedelic LSD to its primary target, the serotonin 2A receptor (5HT2A) given either the AF2 model (orange) or a traditional model (green) of 5HT2A. (A, B) The binding pocket of the AF2 model is more similar (lower root mean squared deviation [RMSD]) than that of the traditional model to the binding pocket of the experimentally determined LSD-bound structure (the ‘reference structure’, white, PDB entry 6WGT). Amino acid residues that differ most from the reference structure are shown in sticks. [SEP] Justify:

Output: The text contrasts the claim by detailing predictions of drug binding poses using different models, specifically highlighting that although the AF2 model has a more similar binding pocket structure, it results in a less accurate prediction (higher RMSD) compared to a traditional model when docking certain ligands. This suggests that not all models, including the economic ones implied in the claim, can accurately predict real-world behavior, as evidenced by the varying accuracy of the predictions from different models depending on the context.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: , 2001 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus Rhamnosus)GGKankainen et al. , 2009 Strain information listed in Supplementary file 3Strain, strain background (Lactiplantibacillus murinus)ASF361Wannemuehler et al. , 2014 Strain information listed in Supplementary file 3Strain, strain background (Enterococcus faecalis)ATCC 29212Minogue et al. , 2014 Strain information listed in Supplementary file 3Strain, strain background (Enterococcus faecalis)ATCC 8459Kopit et al. , 2014 Strain information listed in Supplementary file 3Strain, strain background (Pediococcus pentosaceus)ATCC 25745Makarova et al. , 2006 Strain information listed in Supplementary file 3Strain, strain background (Streptococcus agalactiae)ATCC 27956McDonald and McDonald, 1976 Strain information listed in Supplementary file 3Strain, strain background(Escherichia coli)DH5αTaylor et al. , 1993fhuA2 lac(del)U169 phoA glnV44 Φ80’ lacZ(del) M15 gyrA96 recA1 relA1 endA1 thi−one hsdR17, amplification of cloning vector Strains and culture conditions Request a detailed protocol All strains and plasmids used in this study are listed in Supplementary file 3. Standard laboratory culture medium was used for routine growth of bacteria as follows: Lactiplantibacillus spp. , Lacticaseibacillus spp. , Levilactobacillus brevis, Ligilactobacillus murinus, and Pediococcus pentosaceus, MRS (); Lactococcus lactis and Streptococcus agalactiae, M17 (BD) with 2% w/v glucose; Enterococcus faecalis, and Enterococcus faecium, BHI (BD); and Escherichia coli, LB (). Bacterial strains were incubated without shaking except for E. coli (250 RPM) and at either 30 or 37 °C. Where indicated, strains were grown in filter-sterilized MRS (De MAN et al. [SEP] Justify:

Output: The text does not specifically address the importance of lactic acid bacteria in fermentation processes. It primarily lists various strains of bacteria along with their growth conditions, but lacks any direct connection or discussion regarding their role in fermentation, making it irrelevant to the claim.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: , 2019; Neveu and Rhoden, 2019). is old, its porous interior may have already been completely serpentinized, halting the production of chemical energy sources (Zandanel et al. , 2021). Future missions to this icy moon are necessary to confidently detect life in the subsurface ocean, should it exist. For a more in-depth consideration of Enceladus and its astrobiological relevance, see the recent review by Cable et al. (2020). Considerations for the possibility of life as we don't know it on Enceladus are discussed in 9. 3. 2. 3. 7. 2. 4. 1. Comparison between Enceladus and EuropaEnceladus and Europa share a number of key similarities and differences worthy of note. Both are icy moons known to harbor subsurface liquid water oceans that may be abodes for life. (Anderson et al. , 1998) and Enceladus (Neumann and Kruse, 2019) are likely differentiated. Europa's bulk density and axial moment of inertia imply that it is mostly silicate rock, with a possible iron core and a water + ice layer with a thickness close to just 10% of the body radius (7. 2. 3. 2). Enceladus, in contrast, likely has a porous core of silicates and a water + ice layer with a thickness of up to about 25% of the body radius. Cassini sampling of the plumes of Enceladus implies a high ocean pH as described above. A variety of ocean compositions and pH values have been postulated for Europa's ocean (Zolotov and Kargel, 2009), but there is insufficient evidence to constrain it as yet. Europa's surface is more heavily irradiated than that of Enceladus, thus causing increased oxidation of surface materials from O liberated by photolysis of H2O (Parkinson et al. , 2008; Hand et al. , 2009). Like that of Enceladus, Europa's surface is mostly water ice (Carlson et al. , 2009), but Europa has a large amount of darker material on its surface as well, likely sourced from volcanoes on Io or other endogenous sources (Hand and Carlson, 2015; Hibbitts et al. , 2019). [SEP] Justify:

Output: The text supports the claim by discussing Enceladus and Europa, both of which are icy moons believed to contain subsurface liquid water oceans that may host life. The mentions of the chemical energy sources and the continuing exploration of these celestial bodies indicate a direct connection to astrobiological research aimed at understanding the conditions that could support life beyond Earth.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: (C, D) The LSD-binding pose predicted by docking is less accurate (higher RMSD) when using the AF2 model than when using the traditional model. To further quantify these results, we compare pose prediction accuracy for structures and models with similar binding pocket accuracy. In particular, we calculate pose prediction accuracy as a function of binding pocket accuracy (RMSD) for both experimentally determined structures and models. As expected, we find that average pose prediction accuracy increases as binding pocket accuracy increases (i. e. , RMSD to reference structure decreases). This trend holds for experimentally determined structures, AF2 models, and traditional template-based models (Figure 5 and Figure 5—figure supplement 1). Yet for the same binding pocket accuracy (RMSD from the reference structure), AF2 models yield lower average pose prediction accuracy than experimentally determined structures (Figure 3). In contrast, in cases where traditional models and experimentally determined structures have similar binding pocket accuracies, they yield similar pose prediction accuracies (Figure 5—figure supplement 1). Figure 5 with 1 supplement see all Download asset Open asset Pose prediction accuracy as a function of binding pocket structural accuracy when docking to AlphaFold 2 (AF2) models or experimentally determined structures. Docking to an experimentally determined structure generally leads to more accurate pose prediction than docking to an AF2 model with the same binding pocket root mean squared deviation (RMSD). The difference between the two curves is statistically significant for all binding pocket RMSD values below 1. 1 Å (see Methods). 5—figure supplement 1 for additional data, including results for traditional models and for various docking methods. We also considered the possibility that the improved performance of experimentally determined structures relative to AF2 models might be because, in some cases, the structure used for docking was determined with a bound ligand similar (though not identical) to the ligand being docked. Eliminating such cases from consideration does lead to decreases in both aggregate binding pocket accuracy and pose prediction accuracy of experimentally determined structures, but experimentally determined structures continue to yield significantly more accurate pose predictions than AF2 models (p < 0. 01) (Figure 1—figure supplement 1 and Figure 2—figure supplements 1 and 2). recent papers have concluded that AF2 models fall short of experimentally determined structures when used for ligand docking (Díaz-Rovira et al. , 2023; He et al. [SEP] Justify:

Output: The text contrasts the claim by indicating that the AF2 model is less accurate at predicting pose compared to traditional models, suggesting that not all models (specifically the AF2 model) provide accurate predictions of real-world behavior (in this case, docking accuracy). It highlights that AF2 models yield lower average pose prediction accuracy than experimentally determined structures, thereby supporting the idea that economic models do not uniformly predict real-world behaviors accurately.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: , 1960) lacking beef extract with either 110 mM glucose [gMRS] or 110 mM mannitol [mMRS], or a chemically defined minimal medium (Supplementary file 4) with 125 mM glucose [gCDM] or 125 mM mannitol [mCDM] for 18 hr (Aumiller et al. , 2021). Riboflavin (1 mg/L) was routinely added to the CDM. When indicated, culture medium was supplemented with 20 μg/mL of the quinone 1,4-dihydroxy-2-naphthoic acid (DHNA) (), 1. 25 mM ferric ammonium citrate (C6H8FeNO7) (1. 25 mM) (), riboflavin (Sigma-Aldrich, St. ), or 5 μg/mL erythromycin (VWR). DNA sequence analysis Request a detailed protocol gene locus of L. plantarum NCIMB8826 was identified using NCBI basic local alignment search tool (BLAST) (McGinnis and Madden, 2004) using the L. monocytogenes 10403genes (lmo2634 to lmo2641) as a reference. L. plantarum genes were annotated based on predicted functions within the FLEET pathwa (Light et al. , 2018). FLEET locus genes were identified in other LAB by examining 1,788 complete Lactobacillales genomes available at NCBI (downloaded 02/25/2021). A local BLAST (ver 2. 10. 1) database containing these genomes was queried using tBLASTx with NCIMB8826 FLEET genes a reference. A gene was considered to be present in the Lactobacillales strain genome if the Bit-score was >50 and the E-value was <10–3 (Pearson, 2013). Heatmaps showing the percentage of strains in Lactobacillales genera and the Lactobacillus-genus complex (Zheng et al. , 2020) identified to contain individual FLEET genes were visualized using the R-studio package ggplot2 (Wickham, 2011) with clustering done through UPGMA. loci of L. plantarum strain 8. [SEP] Justify:

Output: The text does not address the role of lactic acid bacteria in fermentation processes. It primarily discusses the culture conditions, gene analysis, and identifiers related to certain strains of L. plantarum and other Lactobacillales without mentioning their importance in fermentation.


Input: Task: corroborate the claim using the given text. Claim: Astrobiology explores the potential for life beyond Earth. [SEP] Text: In contrast, Enceladus has a very bright surface consistent with pure ice plus a small amount of NH3 and tholins in a global coating spread by the action of plumes (Hendrix et al. , 2010). Many lines of evidence have confirmed the presence of plumes at Enceladus, including direct images (Fig. 7. 7), but only intermittent plume activity is expected on Europa as described above. Alternative explanations may account for existing observations instead of plumes (Roth, 2021; Styczinski and Harnett, 2021). Europa is much larger than Enceladus (radii approximately 1560 km and 252 km, respectively), with a higher surface gravity. The ice shell of Enceladus may be as thin as a few kilometers at the south pole (Hemingway and Mittal, 2019), while Europa's stronger gravity likely prevents any conduit from reaching all the way from the ocean to the surface (Rudolph and Manga, 2009). and Enceladus are both thought to have liquid water oceans in contact with silicate rock, they are both promising candidates in the search for life elsewhere. Each may be habitable. What we learn about one moon can sometimes help us understand the other, but we must always keep in mind that Europa is not Enceladus, and vice versa, and exercise caution in studying these bodies. 7. 2. 5. TitanTitan is the largest moon of Saturn, with a radius of 2575 km (50% larger than Earth's moon), and it is the only moon in the with a significant atmosphere. Due to its thick atmosphere (1. 5 bar surface pressure) and accompanying haze p7. 8 shows an image of Titan in front of Saturn, taken by Cassini. FIG. 7. 8. Titan in front of its parent planet Saturn, a natural-color image taken by the Cassini spacecraft. The hazy appearance is the result of the organic-rich haze p7. 9; Hörst et al. , 2012). These organic molecules would fall to the surface, forming the observed dunes, lakes, and seas. mission, scheduled to launch in June 2027, will explore the surface of Titan to characterize the environment and search for signs of life. FIG. 7. 9. Photochemistry in Titan's atmosphere. Energetic photons and charged p7. 1. 5. 4 in the supplementary material). [SEP] Justify:

Output: The text corroborates the claim as it discusses the potential habitability of moons like Enceladus and Europa, indicating that they are promising candidates in the search for life elsewhere. The mention of Titan's exploration for signs of life further supports the claim, reinforcing the idea that astrobiology is concerned with the potential for life beyond Earth.


Input: Task: contrast the claim using the given text. Claim: All economic models accurately predict real-world behavior. [SEP] Text: , 2023; Heo and Feig, 2022; Scardino et al. , 2023). Our results agree with this conclusion but go beyond it in several ways. We compare AF2 models and traditional template-based models, rigorously ensuring that none of these models was informed by experimentally determined structures of the protein being modeled. We find that, in terms of structural accuracy of the binding pocket, AF2 models are much better than traditional models; indeed, the RMSD between an AF2 model and an experimentally determined structure is typically comparable to the RMSD between two structures determined experimentally with different ligands bound. Yet, when used for docking, AF2 models yield pose prediction accuracy similar to that of traditional models and much worse than that of experimentally determined structures. A few caveats are in order. First, building a traditional template-based model is not always possible. We only considered template-based models in cases where a structure was available for another protein with at least 40% sequence identity. However, 80% of human drug targets have at least 50% sequence identity to a protein whose structure was known in 2017 (Somody et al. , 2017), and that number is even higher today. In addition, we note that the traditional models we used were generated relatively quickly by an academic group along with models for hundreds of other proteins. An expert working on a drug discovery project could frequently build a better template-based model—for example, by examining the predictive utility of several models (Carlsson et al. , 2011; Haddad et al. , 2020). Second, our study examined only GPCRs. The results might in principle be different for other classes of drug targets. However, GPCRs have very diverse binding pockets, which have evolved to binding an extremely broad range of ligands, ranging from very small molecules to peptides and proteins, with high specificity (Venkatakrishnan et al. , 2013). Our conclusions thus likely apply to many non-GPCR drug targets—and GPCR targets alone account for roughly half of drug discovery projects. We also note that, for GPCRs specifically, one can often improve docking performance by using a model or an experimentally determined structure in the activation state to which a given ligand preferentially binds (Heo and Feig, 2022; Lee et al. , 2022). [SEP] Justify:

Output: The text contrasts the claim by indicating that while AF2 models show good structural accuracy, their pose prediction accuracy when used for docking is 'much worse' than experimentally determined structures. This suggests that not all models, including those referring to economic domains in a broader context, accurately predict real-world behavior, as evidenced by the limitations of model predictions outlined in the text.


Input: Task: pass the claim using the given text. Claim: Lactic acid bacteria are important for fermentation processes. [SEP] Text: 1 and NCIMB700965 were aligned to the NCIMB8826 genome in Meg(). Insoluble iron reduction assays Request a detailed protocol Cells were collected by centrifugation at 10,000 g for 3 min, washed twice in phosphate-buffered saline (PBS), pH 7. 2 ( and adjusted to an optical density (OD) at 600 nm (OD600nm) of 2 in the presence of 2. 2 mM ferrihydrite (Schwertmann and Fischer, 1973; Stookey, 2002) and 2 mM ferrozine (Sigma-Aldrich). Where indicated, 55 mM glucose or mannitol, 20 μg/mL DHNA, and riboflavin were added. After 3 hr incubation at 30 °C, the cells were collected by centrifugation at 10,000 g for 5 min and the absorbance of the supernatant was measured at 562 nm with a Synergy 2 spectrophotometer (). Quantities of ferrihydrite reduced were determined using a standard curve containing a 2-fold range of FeSO4 (Sigma-Aldrich) (0. 25 mM to 0. 016 mM) and 2 mM ferrozine. The FeSO4 was dissolved in 10 mM cysteine-HCl () to prevent environmental re-oxidation of Fe2+ to Fe3+ in the standard curve. For testing iron reduction activity of cells with a DHNA concentration of 0. 01 μg/mL in the medium, iron(III) oxide nanop5. Splicing-by-overlap extension (SOEing) PCR was used to combine PCR products as previously described (Heckman and Pease, 2007). PCR products were digested with restriction enzymes or SalI () for plasmid ligation and transformation into E. coli DH5α. The resulting plasmids were then introduced to L. plantarum NCIMB8826 by electroporation. Erythromycin-resistant mutants were selected and confirmed for plasmid integration by PCR (see Supplementary file 5 for primer sequences). Subsequently, deletion mutants were identified by a loss of resistance to erythromycin, PCR (see Supplementary file 5 for primer sequences) confirmation, and DNA sequencing ( Bioelectrochemical reactors (BES) construction, operation, and electrochemical techniques Request a detailed protocol L. [SEP] Justify:

Output: The text is largely irrelevant to the claim as it discusses protocols and experimental methods related to iron reduction assays and genetic manipulation of E. coli, without mentioning lactic acid bacteria or fermentation processes. As such, it does not provide any support or contrast to the claim.