Activation of G-protein-coupled receptors (GPCRs) is mediated by molecular switches throughout the transmembrane region of the receptor. In this work, we continued along the path of a previous computational study wherein energy transport in the beta 2 Adrenergic Receptor (beta 2-AR) was examined and allosteric switches were identified in the molecular structure through the reorganization of energy transport networks during activation. In this work, we further investigated the allosteric properties of beta 2-AR, using Protein Contact Networks (PCNs). In this paper, we report an extensive statistical analysis of the topological and structural properties of beta 2-AR along its molecular dynamics trajectory to identify the activation pattern of this molecular system. The results show a distinct character to the activation that both helps to understand the allosteric switching previously identified and confirms the relevance of the network formalism to uncover relevant functional features of protein molecules.
A Statistical Journey through the Topological Determinants of the β2 Adrenergic Receptor Dynamics
Di Paola, Luisa
;Parise, Mauro;
2022-01-01
Abstract
Activation of G-protein-coupled receptors (GPCRs) is mediated by molecular switches throughout the transmembrane region of the receptor. In this work, we continued along the path of a previous computational study wherein energy transport in the beta 2 Adrenergic Receptor (beta 2-AR) was examined and allosteric switches were identified in the molecular structure through the reorganization of energy transport networks during activation. In this work, we further investigated the allosteric properties of beta 2-AR, using Protein Contact Networks (PCNs). In this paper, we report an extensive statistical analysis of the topological and structural properties of beta 2-AR along its molecular dynamics trajectory to identify the activation pattern of this molecular system. The results show a distinct character to the activation that both helps to understand the allosteric switching previously identified and confirms the relevance of the network formalism to uncover relevant functional features of protein molecules.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.