Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.
Sci Rep. 2017 Aug 10;7(1):7828. doi: 10.1038/s41598-017-08224-2.
The most powerful analgesic and addictive properties of opiate alkaloids are mediated by the μ opioid receptor (MOR). The MOR has been extensively investigated as a drug target in the twentieth century, with numerous compounds of varying efficacy being identified. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to identify the binding mechanisms of MORs to BU72 (agonist) and β-funaltrexamine (antagonist). Our approach theoretically suggests that the 34 residues (Lys209-Phe221 and Ile301-Cys321) of the MORs were the key regions enabling the two compounds to bind to the active site of the MORs. When the MORs were in the holo form, the key region was in the open conformation. When the MORs were in the apo form, the key region was in the closed conformation. The key region might be responsible for the selectivity of new MOR agonists and antagonists.
阿片生物碱最强的镇痛和成瘾特性是由 μ 阿片受体（MOR）介导的。MOR 作为 20 世纪的药物靶点得到了广泛研究，发现了许多具有不同疗效的化合物。我们采用分子动力学和高斯加速分子动力学技术，确定了 MOR 与 BU72（激动剂）和 β-纳曲酮（拮抗剂）的结合机制。我们的方法从理论上表明，MOR 的 34 个残基（Lys209-Phe221 和 Ile301-Cys321）是使这两种化合物结合到 MOR 活性位点的关键区域。当 MOR 处于全酶形式时，关键区域处于开放构象。当 MOR 处于apo 形式时，关键区域处于关闭构象。关键区域可能负责新的 MOR 激动剂和拮抗剂的选择性。
