Improved ligand-protein binding affinity predictions using multiple binding modes.

ABSTRACT: Accurate ligand-protein binding affinity prediction, for a set of similar binders, is a major challenge in the lead optimization stage in drug development. In general, docking and scoring functions perform unsatisfactorily in this application. Docking calculations, followed by molecular dynamics simulations and free energy calculations can be applied to improve the predictions. However, for targets with large, flexible binding sites, with no experimentally determined binding modes for a set of ligands, insufficient sampling can decrease the accuracy of the free energy calculations. Cytochrome P450s, a protein family of major importance for drug metabolism, is an example of a challenging target for binding affinity predictions. As a result, the choice of starting structure from the docking

SUBMITTER: Stjernschantz E 

PROVIDER: S-EPMC2877349 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature