SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism
SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism
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DOI：
10.1021/ml100016x
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发表时间：
2010-06-01
影响因子：
4.2
通讯作者：
Olsen, Lars
中科院分区：
文献类型：
--
作者：
Rydberg, Patrik;Gloriam, David E.;Olsen, Lars
SMARTCyp是一种预测细胞色素p450介导的药物样分子代谢位点的计算机方法。该方法首先是一个反应性模型，因此，它显示出预测由细胞色素P450 3A4异构体代谢的位点的偏好。SMARTCyp直接从分子的二维结构预测代谢部位，不需要计算电子性质或生成三维结构。这是一个主要的优势，因为它使SMARTCyp非常快。其他优点是实验数据不是创建模型的先决条件，并且可以很容易地与其他方法集成以创建其他细胞色素P450同工异构体的模型。对394个3A4底物的数据库进行基准测试表明，SMARTCyp在76%的时间内成功识别出排名前两个位置的至少一个代谢位点。SMARTCyp可从http://www.farma.ku.dk/p450下载。
SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism of druglike molecules. The method is foremost a reactivity model, and as such, it shows a preference for predicting sites that are metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of metabolism directly from the 2D structure of a molecule, without requiring calculation of electronic properties or generation of 3D structures. This is a major advantage, because it makes SMARTCyp very fast. Other advantages are that experimental data are not a prerequisite to create the model, and it can easily be integrated with other methods to create models for other cytochrome P450 isoforms. Benchmarking tests on a database of 394 3A4 substrates show that SMARTCyp successfully identifies at least one metabolic site in the top two ranked positions 76% of the time. SMARTCyp is available for download at http://www.farma.ku.dk/p450.