6097645
Simulating Protein Motions with Rigidity Analysis
Protein motions, ranging from molecular flexibility to large-scale conformational change, play an essential role in many biochemical processes. Despite the explosion in our knowledge of structural and functional data, our understanding of protein movement is still very limited. In previous work, we developed and validated a motion planning based method for mapping protein folding pathways from unstructured conformations to the native state. In this paper, we propose a novel method based on rigidity theory to sample conformation space more effectively, and we describe extensions of our framework to automate the process and to map transitions between specified conformations. Our results show that these additions both improve the accuracy of our maps and enable us to study a broader range of motions for larger proteins. For example, we show that rigidity-based sampling results in maps that capture subtle folding differences between protein G and its mutants, NuG1 and NuG2, and we illustrate how our technique can be used to study large-scale conformational changes in calmodulin, a 148 residue signaling protein known to undergo conformational changes when binding to Ca(2+). Finally, we announce our web-based protein folding server which includes a publicly available archive of protein motions: (http://parasol.tamu.edu/foldingserver/).
9601629
Tools for Simulating and Analyzing RNA Folding Kinetics
It has recently been found that some RNA functions are determined by the actual folding kinetics and not just the RNA's nucleotide sequence or its native structure. We present new computational tools for simulating and analyzing RNA folding kinetic metrics such as population kinetics, folding rates, and the folding of particular subsequences. Our method first builds an approximate representation (called a map) of the RNA's folding energy landscape, and then uses specialized analysis techniques to extract folding kinetics from the map. We provide a new sampling strategy called Probabilistic Boltzmann Sampling (PBS) that enables us to approximate the folding landscape with much smaller maps, typically by several orders of magnitude. We also describe a new analysis technique, Map-based Monte Carlo (MMC) simulation, to stochastically extract folding pathways from the map. We demonstrate that our technique can be applied to large RNA (e.g., 200+ nucleotides), where representing the full landscape is infeasible, and that our tools provide results comparable to other simulation methods that work on complete energy landscapes. We present results showing that our approach computes the same relative functional rates as seen in experiments for the relative plasmid replication rates of ColE1 RNAII and its mutants, and for the relative gene expression rates of MS2 phage RNA and its mutants.
8798483
Planning with Reachable Distances: Fast Enforcement of Closure Constraints
Motion planning for closed-chain systems is particularly difficult due to additional closure constraints placed on the system. In fact, the probability of randomly selecting a set of joint angles that satisfy the closure constraints is zero. We propose planning with reachable distance (PRD) to overcome this challenge by first precomputing the subspace satisfying the closure constraints, then directly sampling in it. To do so, we represent the chain as a hierarchy of sub-chains. Then we calculate the "closure" sub-space as appropriate reachable distance ranges of sub-chains satisfying the closure constraints. This provides two distinct advantages over traditional approaches: (1) configurations are quickly sampled and converted to joint angles using basic trigonometry functions instead of more expensive inverse kinematics solvers, and (2) configurations are guaranteed to be closed. In this paper, we describe this hierarchical chain representation and give a sampling algorithm with complexity linear in the number of links. We provide the necessary motion planning primitives for most sampling-based motion planners. Our experimental results show our method is fast, making sampling closed configurations comparable to sampling open chain configurations that ignore closure constraints. Our method is general, easy to implement, and also extends to other distance-related constraints besides the ones demonstrated here
47107463
Using Motion Planning to Study RNA Folding Kinetics
1083190
Streaming media caching algorithms for transcoding proxies
Streaming media is expected to become one of the most popular types of Web content in the future. Due to increasing variety of client devices and the range of access speeds to the Internet, multimedia contents may be required to be transcoded to match the client's capability. With transcoding, both the network and the proxy CPU are potential bottlenecks for streaming media delivery. This paper discusses and compares various caching algorithms designed for transcoding proxies. In particular we propose a new adaptive algorithm that dynamically selects an appropriate metric for adjusting the management policy. Experimental results show that the proposed algorithm significantly outperforms those that cache only untranscoded or only transcoded objects. Moreover motivated by the characteristics of many video compression algorithms, we investigate partitioning a video object into sections based on frame type and handling them individually for proxy caching. It is found that partitioning improves performance when CPU power rather than network bandwidth is the limiting resource, particularly when the reference pattern is not highly skewed.
29395992
Coordinated En-Route Web Caching
Web caching is an important technique for reducing Internet access latency, network traffic, and server load. This paper investigates cache management strategies for the en-route web caching environment, where caches are associated with routing nodes in the network. We propose a novel caching scheme that integrates both object placement and replacement policies and which makes caching decisions on all candidate sites in a coordinated fashion. In our scheme, cache status information along the routing path of a request is used in dynamically determining where to cache the requested object and what to replace if there is not enough space. The object placement problem is formulated as an optimization problem and the optimal locations to cache the object are obtained using a low-cost dynamic programming algorithm. Extensive simulation experiments have been performed to evaluate the proposed scheme in terms of a wide range of performance metrics. The results show that the proposed scheme significantly outperforms existing algorithms which consider either object placement or replacement at individual caches only.
16349513
Analysis of Replica Placement under Expiration-Based Consistency Management
Expiration-based consistency management is widely used to keep replicated contents up-to-date in the Internet. The effectiveness of replication can be characterized by the communication costs of client accesses and consistency management. Both costs depend on the locations of the replicas. This paper investigates the problem of placing replicas in a network where replica consistency is managed by the expiration-based scheme. Our objective is to minimize the total cost of client accesses and consistency management. By analyzing the communication cost of recursive validations for cascaded replicas, we prove that in the optimal placement scheme, the nodes not assigned replicas induce a connected subgraph that includes the origin server. Our results are generic in that they apply to any request arrival patterns. Based on the analysis, an O(D)-time algorithm is proposed to compute the optimal placement of the replicas, where D is the sum of the number of descendants over all nodes in the routing tree
11016588
Optimal hash routing for Web proxies
Hash routing is an effective approach for coordinating a collection of Web proxies. In this paper, we present a comprehensive analytical model for hash routing which takes into consideration a number of factors: the original request distribution, the object allocation strategy, the speeds of the proxies and cache hit ratios. Based on this model, the optimal hash routing problems for static and dynamic client configurations are investigated. Two schemes, OBJ-OPT (OBJect OPTimization) and OBJ/DNS-OPT (OBJect and Domain Name Server OPTimization), are proposed to reduce the response times of Web requests. OBJ-OPT optimizes object allocation under a static client configuration, and OBJ/DNS-OPT optimizes both object and DNS allocations under a dynamic client configuration. Extensive trace-driven simulations have been conducted to evaluate the proposed schemes. The results show that they significantly outperform the intuitive scheme based only on the speeds of the proxies.
2027823
Evolutionary Search for Faces from Line Drawings
Single 2D line drawing is a straightforward method to illustrate 3D objects. The faces of an object depicted by a line drawing give very useful information for the reconstruction of its 3D geometry. Two recently proposed methods for face identification from line drawings are based on two steps: finding a set of circuits that may be faces and searching for real faces from the set according to some criteria. The two steps, however, involve two combinatorial problems. The number of the circuits generated in the first step grows exponentially with the number of edges of a line drawing. These circuits are then used as the input to the second combinatorial search step. When dealing with objects having more faces, the combinatorial explosion prevents these methods from finding solutions within feasible time. This paper proposes a new method to tackle the face identification problem by a variable-length genetic algorithm with a novel heuristic and geometric constraints incorporated for local search. The hybrid GA solves the two combinatorial problems simultaneously. Experimental results show that our algorithm can find the faces of a line drawing having more than 30 faces much more efficiently. In addition, simulated annealing for solving the face identification problem is also implemented for comparison.