Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Zuodaoquanlu No 366, Hongshan District, Wuhan 430073, People's Republic of China.
Eur J Med Chem. 2010 Mar;45(3):967-72. doi: 10.1016/j.ejmech.2009.11.037. Epub 2009 Nov 26.
For better understanding of the molecular interactions of inhibitors with CYP450 1A1, a series of benzoxazoles and benzothiazoles were analyzed by comparative molecular field analysis (CoMFA) and molecular docking. Two conformer-based alignment strategies were employed to construct reliable CoMFA models. The best CoMFA model yielded a predictive correlation coefficient r(2)(pred) value of 0.809. Furthermore, a three-dimensional model of CYP450 1A1 was generated by homology modeling using CYP450 1A2 as a template, and docking of 48 CYP450 1A1 inhibitors into the putative binding sites of the CYP450 1A1 were studied. The results obtained from this study will be helpful in the design of potentially active CYP450 1A1 inhibitors.
为了更好地理解抑制剂与 CYP450 1A1 的分子相互作用，我们通过比较分子场分析（CoMFA）和分子对接对一系列苯并恶唑和苯并噻唑进行了分析。采用了两种基于构象的对齐策略来构建可靠的 CoMFA 模型。最佳的 CoMFA 模型产生了预测相关系数 r(2)(pred)值为 0.809。此外，使用 CYP450 1A2 作为模板通过同源建模生成了 CYP450 1A1 的三维模型，并研究了 48 种 CYP450 1A1 抑制剂在 CYP450 1A1 假定结合位点的对接情况。这项研究的结果将有助于设计潜在的活性 CYP450 1A1 抑制剂。
