Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: Vacuolar ATPases are a potential therapeutic target because of their involvement in a variety of severe diseases such as osteoporosis or cancer. Archazolide A (1) and related analogs have been previously identified as selective inhibitors of V-ATPases with potency down to the sub- nanomolar range. Herein  report on the determination of the ligand binding mode by a combination of molecular dock- ing, molecular dynamics simulations, and biochemical experi- ments, resulting in a sound model for the inhibitory mech- anism of this class of putative anticancer agents. The binding site of archazolides was confirmed to be located in the equatorial region of the membrane-embedded VO-rotor, as recently proposed on the basis of site-directed mutagenesis. Quantification of the bioactivity of a series of archazolide derivatives, together with the docking-derived binding mode of archazolides to the V-ATPase, revealed favorable ligand profiles, which can guide the development of a simplified archazolide analog with potential therapeutic relevance.
['Sandra Dreisigacker', 'Dorota Latek', 'Svenja Bockelmann', 'Markus Huss', 'Helmut Wieczorek', 'Slawomir Filipek', 'Holger Gohlke', 'Dirk Menche', 'Teresa Carlomagno']
I am writing a research paper on a idea Understanding the inhibitory effect of highly potent and selective archazolides binding to the vacuolar ATPase.
[{"from": "human", "value": "I am writing a research paper on a idea Understanding the inhibitory effect of highly potent and selective archazolides binding to the vacuolar ATPase."}, {"from": "gpt", "value": "Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: Vacuolar ATPases are a potential therapeutic target because of their involvement in a variety of severe diseases such as osteoporosis or cancer. Archazolide A (1) and related analogs have been previously identified as selective inhibitors of V-ATPases with potency down to the sub- nanomolar range. Herein  report on the determination of the ligand binding mode by a combination of molecular dock- ing, molecular dynamics simulations, and biochemical experi- ments, resulting in a sound model for the inhibitory mech- anism of this class of putative anticancer agents. The binding site of archazolides was confirmed to be located in the equatorial region of the membrane-embedded VO-rotor, as recently proposed on the basis of site-directed mutagenesis. Quantification of the bioactivity of a series of archazolide derivatives, together with the docking-derived binding mode of archazolides to the V-ATPase, revealed favorable ligand profiles, which can guide the development of a simplified archazolide analog with potential therapeutic relevance."}]