Modeling Ligand Binding Site Water Networks with Site Identification by Ligand Competitive Saturation: Impact on Ligand Binding Orientations and Relative Binding Affinities.

ABSTRACT: Appropriate treatment of water contributions to protein-ligand interactions is a very challenging problem in the context of adequately determining the number of waters to investigate and undertaking conformational sampling of the ligands, the waters, and the surrounding protein. In the present study, an extension of the Site Identification by Ligand Competitive Saturation-Monte Carlo (SILCS-MC) docking approach is presented that enables the determination of the location of water molecules in the binding pocket and their impact on the predicted ligand binding orientation and affinities. The approach, termed SILCS-WATER, involves MC sampling of the ligand along with explicit water molecules in a binding site followed by selection of a subset of waters within specified energetic and distance

SUBMITTER: Kumar A 

PROVIDER: S-EPMC11668617 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature