Cheminformatics meets molecular mechanics: a combined application of knowledge-based pose scoring and physical force field-based hit scoring functions improves the accuracy of structure-based virtual screening.

ABSTRACT: Poor performance of scoring functions is a well-known bottleneck in structure-based virtual screening (VS), which is most frequently manifested in the scoring functions' inability to discriminate between true ligands vs known nonbinders (therefore designated as binding decoys). This deficiency leads to a large number of false positive hits resulting from VS. We have hypothesized that filtering out or penalizing docking poses recognized as non-native (i.e., pose decoys) should improve the performance of VS in terms of improved identification of true binders. Using several concepts from the field of cheminformatics, we have developed a novel approach to identifying pose decoys from an ensemble of poses generated by computational docking procedures. We demonstrate that the use of target-speci

SUBMITTER: Hsieh JH 

PROVIDER: S-EPMC3264743 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature