Paper Citing NAMD - Abstract
Bai, Qifeng; Zhang, Yang; Ban, Yihe; Liu, Huanxiang; Yao, Xiaojun
Computational Study on the Different Ligands Induced Conformation Change of beta 2 Adrenergic Receptor-Gs Protein Complex
PLOS ONE, 8 Art. No. e68138, JUL 29 2013
beta(2) adrenergic receptor (beta(2)AR) regulated many key physiological processes by activation of a heterotrimeric GTP binding protein (Gs protein). This process could be modulated by different types of ligands. But the details about this modulation process were still not depicted. Here, we performed molecular dynamics (MD) simulations on the structures of beta(2)AR-Gs protein in complex with different types of ligands. The simulation results demonstrated that the agonist BI-167107 could form hydrogen bonds with Ser203(5.42), Ser207(5.46) and Asn293(6.55) more than the inverse agonist ICI 118,551. The different binding modes of ligands further affected the conformation of beta(2)AR. The energy landscape profiled the energy contour map of the stable and dissociated conformation of G alpha s and G alpha gamma when different types of ligands bound to beta(2)AR. It also showed the minimum energy pathway about the conformational change of G alpha s and G beta gamma along the reaction coordinates. By using interactive essential dynamics analysis, we found that G alpha s and G beta gamma domain of Gs protein had the tendency to separate when the inverse agonist ICI 118,551 bound to beta(2)AR. The alpha 5-helix had a relatively quick movement with respect to transmembrane segments of beta(2)AR when the inverse agonist ICI 118,551 bound to beta(2)AR. Besides, the analysis of the centroid distance of G alpha s and G beta gamma showed that the G alpha s was separated from G beta gamma during the MD simulations. Our results not only could provide details about the different types of ligands that induced conformational change of beta(2)AR and Gs protein, but also supplied more information for different efficacies of drug design of beta(2)AR.
