Van Damme Sofie, Bultinck Patrick
Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 S-3, B-9000 Gent, Belgium.
J Comput Chem. 2009 Sep;30(12):1749-57. doi: 10.1002/jcc.21177.
Structure-activity relationships of 46 P450 2A6 inhibitors were analyzed using the 3D-QSAR methodology. The analysis was carried out to confront the use of traditional steric and electrostatic fields with that of a number of fields reflecting conceptual DFT properties: electron density, HOMO, LUMO, and Fukui f- function as 3D fields. The most predictive models were obtained by combining the information of the electron density with the Fukui f- function (r2 = 0.82, q2 = 0.72), yielding a statistically significant and predictive model. The generated model was able to predict the inhibition potencies of an external test set of five chemicals. The result of the analysis indicates that conceptual DFT-based molecular fields can be useful as 3D QSAR molecular interaction fields.
使用3D-QSAR方法分析了46种细胞色素P450 2A6抑制剂的构效关系。进行该分析是为了将传统的空间和静电场与一些反映概念性密度泛函理论（DFT）性质的场进行对比：电子密度、最高占据分子轨道（HOMO）、最低未占分子轨道（LUMO）以及作为三维场的福井f函数。通过将电子密度信息与福井f函数相结合，获得了预测性最强的模型（r2 = 0.82，q2 = 0.72），得到了一个具有统计学显著性和预测性的模型。生成的模型能够预测一组包含五种化学物质的外部测试集的抑制效力。分析结果表明，基于概念性DFT的分子场可作为3D QSAR分子相互作用场。
