Dissociation kinetics of G proteins from G protein-coupled receptors and effects of allosteric modulation.

ABSTRACT: G protein-coupled receptors (GPCRs), the largest superfamily of human membrane proteins with >800 members, are primary targets for ~1/3 of all marketed drugs. Recent fluorescence experiments underscored the pivotal role of GPCR-G protein complex lifetime in their coupling efficiency and selectivity. However, these experiments are often expensive, time-consuming, and limited to a small number of GPCR-G protein systems. On the other hand, it is challenging to simulate GPCR-G protein dissociation using molecular dynamics (MD) methods. Here, we have employed Protein-Protein Interaction Gaussian accelerated MD (PPI-GaMD) simulations and experiments to probe the kinetics and pathways of G protein dissociation from GPCRs. For five systems with published experimental kinetic data, PPI-GaMD simulat

SUBMITTER: Wang J 

PROVIDER: S-EPMC12646235 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature