Undirected Exploration of Binding Pockets with Flexible Topology.

ABSTRACT: A common first step in drug design is virtual high-throughput screening (VHTS), where a large number of potential drug molecules are computationally modeled in a protein binding pocket and filtered down to a smaller set of hits that can be further tested computationally or experimentally. Traditional strategies for VHTS do not account for ligand-induced conformational changes in proteins as they typically rely on a single static structure to represent the protein. This neglects the role of binding entropy and the fact that different ligand molecules can induce slightly different conformations in the protein binding site that significantly affect the assessment of a given molecule's fit. To address this challenge, we have developed a method called "flexible topology", where a subset of atom

SUBMITTER: Fathi Niazi F 

PROVIDER: S-EPMC12573749 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature