Assessing Genetic Algorithm-Based Docking Protocols for Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins.

ABSTRACT: Although molecular docking has evolved dramatically over the years, its application to glycosaminoglycans (GAGs) has remained challenging because of their intrinsic flexibility, highly anionic character and rather ill-defined site of binding on proteins. GAGs have been treated as either fully "rigid" or fully "flexible" in molecular docking. We reasoned that an intermediate semi-rigid docking (SRD) protocol may be better for the recapitulation of native heparin/heparan sulfate (Hp/HS) topologies. Herein, we study 18 Hp/HS-protein co-complexes containing chains from disaccharide to decasaccharide using genetic algorithm-based docking with rigid, semi-rigid, and flexible docking protocols. Our work reveals that rigid and semi-rigid protocols recapitulate native poses for longer chains (5→10

SUBMITTER: Holmes SG 

PROVIDER: S-EPMC10669598 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature