Datar Prasanna A, Coutinho Evans C
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India.
J Mol Graph Model. 2004 Dec;23(3):239-51. doi: 10.1016/j.jmgm.2004.07.003.
A diverse set of 53 cyclooxygenase-2 (COX-2) inhibitors which were aligned in two different ways were subjected to CoMFA analysis. The first method of alignment of the molecules was based on the binding information sourced from the crystallographic study, from which CoMFA Model 1 was derived. The second mode of alignment was generated by docking the inhibitors in the binding pocket using the DOCK and AFFINITY suite of programs; this gave a second model. The CoMFA Model 2 was slightly better than Model 1 in terms of the statistical parameters r(2) and q(2). The two models could predict very well the activity of a test set of diverse molecules, with a predictive r(2) of 0.593 and 0.768, respectively. Besides the QSAR results, the docking studies give a deep insight into the H-bonding interactions between the inhibitors and residues in the active site of the enzyme, which can be exploited in designing better inhibitors. Useful ideas on activity improvement could be gleaned from these models.
一组53种以两种不同方式排列的环氧化酶-2（COX-2）抑制剂接受了比较分子场分析（CoMFA）。分子的第一种排列方法基于晶体学研究获得的结合信息，由此得出CoMFA模型1。第二种排列方式是使用DOCK和AFFINITY程序套件将抑制剂对接至结合口袋中生成的；这产生了第二个模型。就统计参数r(2)和q(2)而言，CoMFA模型2略优于模型1。这两个模型能够很好地预测一组不同分子的测试集的活性，预测r(2)分别为0.593和0.768。除了定量构效关系（QSAR）结果外，对接研究还深入了解了抑制剂与酶活性位点残基之间的氢键相互作用，这可用于设计更好的抑制剂。可以从这些模型中收集到关于活性改善的有用想法。
