A Statistical Journey through the Topological Determinants of the β2 Adrenergic Receptor Dynamics

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.

Automated summary

This research investigates the activation of G-protein-coupled receptors through molecular switches and studies the allosteric properties of beta 2-AR using Protein Contact Networks. The statistical analysis of topological and structural properties along the molecular dynamics trajectory reveals the activation pattern and emphasizes the significance of network formalism in uncovering functional features of protein molecules.