| Abstract
| - This study addresses a number of topical issues around the use of protein−ligand docking in virtual screening.We show that, for the validation of such methods, it is key to use focused libraries (containing compoundswith one-dimensional properties, similar to the actives), rather than “random” or “drug-like” libraries to testthe actives against. We also show that, to obtain good enrichments, the docking program needs to producereliable binding modes. We demonstrate how pharmacophores can be used to guide the dockings and improveenrichments, and we compare the performance of three consensus-ranking protocols against ranking basedon individual scoring functions. Finally, we show that protein−ligand docking can be an effective aid in thescreening for weak, fragment-like binders, which has rapidly become a popular strategy for hit identification.All results presented are based on carefully constructed virtual screening experiments against four targets,using the protein−ligand docking program GOLD.
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