Mind the Gap-Deciphering GPCR Pharmacology Using 3D Pharmacophores and Artificial Intelligence.

ABSTRACT: G protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant and well-studied protein targets, yet unanswered questions in the field leave significant gaps in our understanding of their nuanced structure and function. Three-dimensional pharmacophore models are powerful computational tools in in silico drug discovery, presenting myriad opportunities for the integration of GPCR structural biology and cheminformatics. This review highlights success stories in the application of 3D pharmacophore modeling to de novo drug design, the discovery of biased and allosteric ligands, scaffold hopping, QSAR analysis, hit-to-lead optimization, GPCR de-orphanization, mechanistic understanding of GPCR pharmacology and the elucidation of ligand-receptor interactions. Furthermore

SUBMITTER: Noonan T 

PROVIDER: S-EPMC9695541 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature