期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 46, 期 6, 页码 1066-1080出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm020269o
关键词
-
资金
- NIEHS NIH HHS [P30-ESO5707, P42-ES04699, R37-ES02710] Funding Source: Medline
A data set of 348 urea-like compounds that inhibit the soluble epoxide hydrolase enzyme in mice and humans is examined. Compounds having IC50 values ranging from 0.06 to > 500 muM (murine) and 0.10 to > 500 muM (human) are categorized as active or inactive for classification, while quantitation is performed on smaller compound subsets ranging from 0.07 to 431,muM (murine) and 0.11 to 490 muM (human). Each compound is represented by calculated structural descriptors that encode topological, geometrical, electronic, and polar surface features. Multiple linear regression (MLR) and computational neural networks (CNNs) are employed for quantitative models. Three classification algorithms, k-nearest neighbor (kNN), linear discriminant analysis (LDA), and radial basis function neural networks (RBFNN), are used to categorize compounds as active or inactive based on selected data split points. Quantitative modeling of human enzyme inhibition results in a nonlinear, five-descriptor model with root-mean-square errors (log units of IC50 [muM]) of 0.616 (r(2) = 0.66), 0.674 (r(2) = 0.61), and 0.914 (r(2) = 0.33) for training, cross-validation, and prediction sets, respectively. The best classification results for human and murine enzyme inhibition are found using kNN. Human classification rates using a seven-descriptor model for training and prediction sets are 89.1% and 91.4%, respectively. Murine classification rates using a five-descriptor model for training and prediction sets are 91.5% and 88.6%, respectively.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据