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

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.