Energy Transport in Class B GPCRs: Role of Protein–Water Dynamics and Activation

Autor:	Humanath Poudel, David M. Leitner
Rok vydání:	2022
Předmět:	Rhodopsin Materials Chemistry Water Physical and Theoretical Chemistry Ligands Peptides Glucagon-Like Peptide-1 Receptor Receptors G-Protein-Coupled Surfaces Coatings and Films
Zdroj:	The Journal of Physical Chemistry B. 126:8362-8373
ISSN:	1520-5207 1520-6106
Popis:	We compute energy exchange networks (EENs) through glucagon-like peptide-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR), in inactive and two active states, one activated by a peptide ligand and the other by a small molecule agonist, from results of molecular dynamics simulations. The reorganized network upon activation contains contributions from structural as well as from dynamic changes and corresponding entropic contributions to the free energy of activation, which are estimated in terms of the change in rates of energy transfer across non-covalent contacts. The role of water in the EENs and in activation of GLP-1R is also investigated. The dynamics of water in contact with the central polar network of the transmembrane region is found to be significantly slower for both activated states compared to the inactive state. This result is consistent with the contribution of water molecules to activation of GLP-1R previously suggested and resembles water dynamics in parts of the transmembrane region found in earlier studies of rhodopsin-like GPCRs.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4447d1736b8fc892bb8611ea08f8d634 https://doi.org/10.1021/acs.jpcb.2c03960 Zobrazit plný text záznamu