Modeling K(m) values using electrotopological state: substrates for cytochrome P450 3A4-mediated metabolism.
In order to determine K(m) values of substrates for CYP3A4-mediated metabolism, an in silico model has been developed in the present work. Using electrotopological state (E-state) indices, together with Bayesian-regularized neural network (BRNN), we have described an in silico method to model log(1/K(m)) values of various substrates. The relative importance of the E-state indices is analyzed by principal component analysis. By using an additional external test set, which is independent of the training set, the robustness and predictivity of the model are also validated.
Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Graduate School of the Chinese Academy of Sciences, #457 Zhongshan Road, Dalian 116023, China.
Yong-Hua
YH
Wang
Yan
Y
Li
Yan-Hong
YH
Li
Sheng-Li
SL
Yang
Ling
L
Yang
D019295:Computational Biology; D003511:Cyclohexanols / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D025341:Principal Component Analysis; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D013379:Substrate Specificity; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D011763:Pyrrolizidine Alkaloids; D000069470:Venlafaxine Hydrochloride; D003577:Cytochrome P-450 Enzyme System; C009237:senecionine; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human