a Center for Biomarkers and Biotech Drugs , Kaohsiung Medical University , Kaohsiung , Taiwan.
b Department of Biochemistry, School of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.
J Biomol Struct Dyn. 2019 Jan;37(1):166-177. doi: 10.1080/07391102.2017.1422025. Epub 2018 Jan 7.
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.
G 蛋白偶联受体在各种信号通路中发挥着关键作用，并作为治疗广泛疾病的靶点。自 20 世纪以来，人们对μ阿片受体（MOR）作为药物靶点进行了广泛的研究。我们使用增强采样方法（高斯加速分子动力学）、结合口袋位点面积方法、均方根偏差方法和自由能（平均力势）方法研究了 MOR 的失活和激活过程。本研究揭示了两种重要的中间 MOR 结构（中间和中间失活），结果表明中间 MOR 结构负责阿片类药物的选择性。
