The computational model to predict accurately inhibitory activity for inhibitors towards CYP3A4.
The cytochrome P450 (CYP) is a superfamily of enzymes with oxidative function responsible for the metabolism of xenobiotics especially drug metabolism. CYP3A4, an extensive studied CYP isoform, plays crucial role in the metabolism of structurally diverse drugs. Furthermore, the drug-drug interaction resulted from the inhibition of CYP3A4 activity is of extreme importance for the treatment of disease and the development of new drug. In this study, using the method of the support vector machine (SVM) and three descriptors selected from the 153 descriptors we construct the models that can predict accurately the inhibitory effect of a compound on the activity of CYP3A4. By optimizing the parameters related to SVM, the cross validation correlation efficient of the model can achieve 0.71, which is higher than those of other models obtained using Artifical Neutral Network (ANN) and Partial least square (PLS) methods to our knowledge, and thus our model can present the important application in assessment of the potential toxicity of a drug as well as prediction of drug-drug interactions.
College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China.
Zhiyuan
Z
Xie
Tao
T
Zhang
Jing-Fang
JF
Wang
Kuo-Chen
KC
Chou
Dong-Qing
DQ
Wei
D051544:Cytochrome P-450 CYP3A / Q000737:chemistry*; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D016571:Neural Networks, Computer
D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human