Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.

ABSTRACT: Molecular docking methods are widely used in drug discovery efforts. RAS proteins are important cancer drug targets, and are useful systems for evaluating docking methods, including accounting for solvation effects and covalent small molecule binding. Water often plays a key role in small molecule binding to RAS proteins, and many inhibitors─including FDA-approved drugs─covalently bind to oncogenic RAS proteins. We assembled a RAS test set, consisting of 138 RAS protein structures and 2 structures of KRAS DNA in complex with ligands. In DOCK 6, we have implemented a receptor desolvation scoring function and a covalent docking algorithm. These new features were evaluated using the test set, with pose reproduction, cross-docking, and enrichment calculations. We tested two solvation methods f

SUBMITTER: Tan YS 

PROVIDER: S-EPMC11776051 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature