Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Austria.
Adv Drug Deliv Rev. 2015 Jun 23;86:61-71. doi: 10.1016/j.addr.2015.04.020. Epub 2015 May 6.
Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabolites these enzymes generate. In recent years, many different in silico approaches have been developed to predict binding or regioselective product formation for the different CYP isoforms. These comprise ligand-based methods that are trained on experimental CYP data and structure-based methods that consider how the substrate is oriented in the active site or/and how reactive the part of the substrate that is accessible to the heme group is. We will review key aspects for various approaches that are available to predict binding and site of metabolism (SOM), what outcome can be expected from the predictions, and how they could potentially be improved.
细胞色素 P450 酶（CYPs）构成了参与外源物质代谢的最重要的酶家族之一。CYPs 包含许多同工酶，它们催化各种各样的反应，并且可能形成大量不同的代谢物。然而，通常很难推断出这些酶产生的代谢物是什么。近年来，已经开发出许多不同的计算方法来预测不同 CYP 同工酶的结合或区域选择性产物形成。这些方法包括基于配体的方法，这些方法是根据实验 CYP 数据进行训练的，以及基于结构的方法，这些方法考虑了底物在活性部位的定向方式，以及可及到血红素基团的底物部分的反应性如何。我们将回顾可用于预测结合和代谢部位（SOM）的各种方法的关键方面，从预测中可以预期到什么结果，以及它们如何可能得到改进。
