Rydberg Patrik, Gloriam David E, Zaretzki Jed, Breneman Curt, Olsen Lars
Biostructural Research, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York 12180.
ACS Med Chem Lett. 2010 Mar 15;1(3):96-100. doi: 10.1021/ml100016x. eCollection 2010 Jun 10.
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.
SMARTCyp是一种计算机模拟方法，用于预测细胞色素P450介导的类药物分子代谢位点。该方法首先是一个反应性模型，因此，它在预测由细胞色素P450 3A4同工型代谢的位点方面表现出偏好。SMARTCyp直接从分子的二维结构预测代谢位点，无需计算电子性质或生成三维结构。这是一个主要优点，因为它使SMARTCyp非常快速。其他优点是创建模型不需要实验数据，并且它可以很容易地与其他方法集成，以创建针对其他细胞色素P450同工型的模型。对394种3A4底物数据库进行的基准测试表明，SMARTCyp在76%的情况下成功地在前两个排名位置识别出至少一个代谢位点。可在http://www.farma.ku.dk/p450下载SMARTCyp。
