The comparative molecular surface analysis (CoMSA) with modified uniformative variable elimination-PLS (UVE-PLS) method: Application to the steroids binding the aromatase enzyme

被引:48
作者
Polanski, J [1 ]
Gieleciak, R [1 ]
机构
[1] Silesian Univ, Inst Chem, Dept Organ Chem, PL-40006 Katowice, Poland
来源
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES | 2003年 / 43卷 / 02期
关键词
D O I
10.1021/ci020038q
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The application of the CoMSA method to analyze 3D QSAR of 50 steroid aromatase inhibitors is described. The 3D QSAR model obtained, reaching a value of cross-validated q(2) = 0.96 (s = 0.31), significantly outperforms those reported in the literature for the CoMFA or CoSA (CoSASA). It is shown that the Uniformative Variable Elimination UVE-PLS or modified iterative UVE procedure (IVE-PLS) can be used for indicating the regions contributing to the binding activity. Thus, after separating the series into two groups of the training and test molecules quite correct external predictions result from the processing of the training set. We proved that the procedure of the data elimination provides stable results, if tested in 50 random runs of the IVE-PLS-CoMSA with different training/test sets. Depending upon the procedure used the quality of the predictions for 25 test molecules is given by SDEP = (Sigma(y(pred)-y(obs))(2)/n)(1/2) = 0.321 - 0.782.
引用
收藏
页码:656 / 666
页数:11
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