Engineering G protein-coupled receptors for stabilization.

ABSTRACT: G protein-coupled receptors (GPCRs) are one of the most important families of targets for drug discovery. One of the limiting steps in the study of GPCRs has been their stability, with significant and time-consuming protein engineering often used to stabilize GPCRs for structural characterization and drug screening. Unfortunately, computational methods developed using globular soluble proteins have translated poorly to the rational engineering of GPCRs. To fill this gap, we propose GPCR-tm, a novel and personalized structurally driven web-based machine learning tool to study the impacts of mutations on GPCR stability. We show that GPCR-tm performs as well as or better than alternative methods, and that it can accurately rank the stability changes of a wide range of mutations occurring in v

SUBMITTER: Velloso JPL 

PROVIDER: S-EPMC11094779 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature