Vibrational energy landscapes and energy flow in GPCRs: comparison between class A and class B GPCRs using all atom and coarse-grained models

Abstract

We compare vibrational energy landscapes and dynamics of the glucagon-like peptide 1 receptor (GLP-1R), a class B G-protein coupled receptor (GPCR), with corresponding properties of a class A GPCR studied previously. Energy flow in GLP-1R is computed by molecular dynamics (MD) simulations in active and inactive states using all atom (AA) and coarse-grained (CG) models. Based on the MD data, we construct and analyze the vibrational energy landscape of GLP-1R, focusing on the relative free energy of each residue and the minimum free energy barriers for energy transfer between them. We find that prolines and glycines, which contribute to GLP-1R plasticity and function, are bottlenecks to energy transport along the backbone, causing diversion of energy through alternative pathways via nearby noncovalent contacts. The probability distributions for the energy transfer time between numerous pairs of amino acids are computed, revealing pathways for energy transport that include noncovalent contacts connecting different helices. These distributions and mean energy transfer times are similar for the AA and CG models, validating the CG representation for future applications.