Identifying Artifacts from Large Library Docking.

ABSTRACT: While large library docking has discovered potent ligands for multiple targets, as the libraries have grown, the very top of the hit-lists can become populated with artifacts that cheat our scoring functions. Though these cheating molecules are rare, they become ever-more dominant with library growth. Here, we investigate rescoring top-ranked molecules from docking screens with orthogonal methods to identify these artifacts, exploring implicit solvent models and absolute binding free energy perturbation (AB-FEP) as cross-filters. In retrospective studies, this approach deprioritized high-ranking non-binders for nine targets while leaving true ligands relatively unaffected. We tested the method prospectively against results from large library docking AmpC β-lactamase. From the very t

SUBMITTER: Wu Y 

PROVIDER: S-EPMC11275789 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature