Fragment-centric topographic mapping method guides the understanding of ABCG2-inhibitor interactions.

ABSTRACT: Understanding protein-ligand interactions is crucial to drug discovery and design. However, it would be extremely difficult for the proteins which only have one available apo structure but multiple binding sites. To address this constraint, a fragment-centric topographic mapping method (AlphaSpace software) was employed to map out concave interaction pockets at the assigned protein region. These pockets are used as complementary spaces to screen the known inhibitors for this specific binding site and to guide the molecular docking pose selection as well as protein-ligand interaction analysis. By mapping the shape of central cavity surface, we have tested the strategy against a multi-drug resistant transmembrane protein-ABCG2 to assist in generating a pharmacophore model for its inhibitors

SUBMITTER: Wu Y 

PROVIDER: S-EPMC9061187 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature