Improving the Modeling of Extracellular Ligand Binding Pockets in RosettaGPCR for Conformational Selection.

ABSTRACT: G protein-coupled receptors (GPCRs) are the largest class of drug targets and undergo substantial conformational changes in response to ligand binding. Despite recent progress in GPCR structure determination, static snapshots fail to reflect the conformational space of putative binding pocket geometries to which small molecule ligands can bind. In comparative modeling of GPCRs in the absence of a ligand, often a shrinking of the orthosteric binding pocket is observed. However, the exact prediction of the flexible orthosteric binding site is crucial for adequate structure-based drug discovery. In order to improve ligand docking and guide virtual screening experiments in computer-aided drug discovery, we developed RosettaGPCRPocketSize. The algorithm creates a conformational ensemble of biop

SUBMITTER: Liessmann F 

PROVIDER: S-EPMC10178219 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature