In silico studies of conformational dynamics of Mu opioid receptor performed using gaussian accelerated molecular dynamics

Jun-Min Liao; Yeng-Tseng Wang

doi:10.1080/07391102.2017.1422025

In silico studies of conformational dynamics of Mu opioid receptor performed using gaussian accelerated molecular dynamics

J Biomol Struct Dyn. 2019 Jan;37(1):166-177. doi: 10.1080/07391102.2017.1422025. Epub 2018 Jan 7.

Authors

Jun-Min Liao¹, Yeng-Tseng Wang^{1

2

3}

Affiliations

¹ a Center for Biomarkers and Biotech Drugs , Kaohsiung Medical University , Kaohsiung , Taiwan.
² b Department of Biochemistry, School of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.
³ c Graduate Institute of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.

PMID: 29277141
DOI: 10.1080/07391102.2017.1422025

Abstract

G-protein-coupled receptors play a crucial role in various signaling pathways and function as targets for treating a wide spectrum of diseases. Since the twentieth century, extensive research has been conducted on the Mu opioid receptor (MOR) as a drug target. We examined the MOR inactivation and activation processes using an enhanced sampling method (Gaussian accelerated molecular dynamics), the binding pocket site area method, the root mean square deviation method, and the free energy (potential of mean force) method. This study revealed two important intermediate MOR structures (intermediate and intermediate inactive), and the results suggest that the intermediate MOR structure is responsible for the selectivity of opioids.

Keywords: Gaussian-accelerated molecular dynamics; Mu opioid receptor; intermediate; potential of mean force.

MeSH terms

Algorithms
Binding Sites
Models, Molecular
Molecular Dynamics Simulation*
Protein Binding
Protein Conformation*
Protein Interaction Domains and Motifs
Receptors, Opioid, mu / chemistry*
Structure-Activity Relationship

Substances

Receptors, Opioid, mu