当前位置：
X-MOL 学术
›
Chem. Bio. Drug Des.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Computational studies on horseshoe shape pocket of human orexin receptor type 2 and boat conformation of suvorexant by molecular dynamics simulations
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2018-03-08 , DOI: 10.1111/cbdd.13181 Qifeng Bai 1 , Horacio Pérez-Sánchez 2 , Zhuoyu Shi 1 , Lanlan Li 3 , Danfeng Shi 3 , Huanxiang Liu 1 , Xiaojun Yao 1, 3
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2018-03-08 , DOI: 10.1111/cbdd.13181 Qifeng Bai 1 , Horacio Pérez-Sánchez 2 , Zhuoyu Shi 1 , Lanlan Li 3 , Danfeng Shi 3 , Huanxiang Liu 1 , Xiaojun Yao 1, 3
Affiliation
|
The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX2R with the boat conformation. The horseshoe shape pocket plays an important role on the biological activity of OX2R in the cell membrane. To study the binding mechanism between the horseshoe shape pocket of OX2R and boat conformation of suvorexant, the crystal structures of wild type and N324A mutant of OX2R in complex with antagonist suvorexant are chosen to perform molecular dynamics (MD) simulations, QM/MM, and MMGBSA calculations. By comparison with the wild type of OX2R, the results show the 1,2,3‐triazole and p‐toluamide groups of suvorexant are changed in the N324A mutant of OX2R during 200 ns MD simulations. The QM/MM and weak interaction analysis are employed to calculate the non‐covalent bonds interaction between suvorexant and key residues in the wild type and N324A mutant of OX2R. The MMGBSA calculations indicate the entropy energy is an important influence factor for suvorexant affinity in the distorted horseshoe shape pocket of OX2R. Our results not only show the horseshoe shape pocket of OX2R is the necessary conformation for the binding of antagonist suvorexant, but also give the important sites and structural features for antagonist design of OX2R.
中文翻译：
通过分子动力学模拟研究人食欲素2型受体的马蹄形袋和suvorexant的船形
FDA批准的suvorexant药物以船形与OX 2 R的马蹄形袋结合。马蹄形袋对细胞膜中OX 2 R的生物活性起着重要作用。为了研究OX 2 R的马蹄形口袋与suvorexant的船形之间的结合机理，选择野生型和OX 2 R的N324A突变体与拮抗剂suvorexant配合物的晶体结构进行分子动力学（MD）模拟，QM / MM和MMGBSA计算。通过与野生型OX 2 R进行比较，结果表明，在OX 2 N324A突变体中，suvorexant的1,2,3-三唑和对甲苯胺基团发生了变化在200 ns MD仿真期间为R。使用QM / MM和弱相互作用分析来计算野生型和OX 2 R的N324A突变体中suvorexant和关键残基之间的非共价键相互作用。MMGBSA计算表明熵能是suvorexant亲和力的重要影响因素在OX扭曲马蹄形口袋2 R.我们的研究结果不仅显示OX的马蹄形口袋2 R代表拮抗剂的suvorexant的结合必要的形态，但也给了OX的拮抗剂设计中的重要部位和结构特点2 R.
更新日期：2018-03-08
中文翻译：
通过分子动力学模拟研究人食欲素2型受体的马蹄形袋和suvorexant的船形
FDA批准的suvorexant药物以船形与OX 2 R的马蹄形袋结合。马蹄形袋对细胞膜中OX 2 R的生物活性起着重要作用。为了研究OX 2 R的马蹄形口袋与suvorexant的船形之间的结合机理，选择野生型和OX 2 R的N324A突变体与拮抗剂suvorexant配合物的晶体结构进行分子动力学（MD）模拟，QM / MM和MMGBSA计算。通过与野生型OX 2 R进行比较，结果表明，在OX 2 N324A突变体中，suvorexant的1,2,3-三唑和对甲苯胺基团发生了变化在200 ns MD仿真期间为R。使用QM / MM和弱相互作用分析来计算野生型和OX 2 R的N324A突变体中suvorexant和关键残基之间的非共价键相互作用。MMGBSA计算表明熵能是suvorexant亲和力的重要影响因素在OX扭曲马蹄形口袋2 R.我们的研究结果不仅显示OX的马蹄形口袋2 R代表拮抗剂的suvorexant的结合必要的形态，但也给了OX的拮抗剂设计中的重要部位和结构特点2 R.
京公网安备 11010802027423号