Comparative Study of Allosteric GPCR Binding Sites and Their Ligandability Potential.

ABSTRACT: The steadily growing number of experimental G-protein-coupled receptor (GPCR) structures has revealed diverse locations of allosteric modulation, and yet few drugs target them. This gap highlights the need for a deeper understanding of allosteric modulation in GPCR drug discovery. The current work introduces a systematic annotation scheme to structurally classify GPCR binding sites based on receptor class, transmembrane helix contacts, and, for membrane-facing sites, membrane sublocation. This GPCR specific annotation scheme was applied to 107 GPCR structures bound by small molecules contributing to 24 distinct allosteric binding sites for comparative evaluation of three binding site detection methods (BioGPS, SiteMap, and FTMap). BioGPS identified the most in 22 of 24 sites. In addition,

SUBMITTER: Peter S 

PROVIDER: S-EPMC11558664 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature