Cytochromes P450 are a class of metalloproteins which are responsible for electron transfer in a wide spectrum of reactions including metabolic biotransformation of endogenous and exogenous substrates. The superfamily of cytochromes P450 consists of families and subfamilies which are characterized by a specific structure and substrate specificity. Cytochromes P450 family 1 (CYP1s) play a distinctive role in the metabolism of drugs and chemical procarcinogens. In recent decades, these hemoproteins have been intensively studied with the use of computational methods which have been recently developed remarkably to be used in the process of drug design by the virtual screening of compounds in order to find agents with desired properties. Moreover, the molecular modeling of proteins and ligand docking to their active sites provide an insight into the mechanism of enzyme action and enable us to predict the sites of drug metabolism. The review presents the current status of knowledge about the use of the computational approach in studies of ligand-enzyme interactions for CYP1s. Research on the metabolism of substrates and inhibitors of CYP1s and on the selectivity of their action is particularly valuable from the viewpoint of cancer chemoprevention, chemotherapy, and drug-drug interactions.

中文翻译：

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细胞色素P450家族1抑制剂的基于结构的药物设计。

细胞色素P450是一类金属蛋白，负责在广泛的反应中转移电子，包括内源性和外源性底物的代谢生物转化。细胞色素P450的超家族由具有特定结构和底物特异性的家族和亚家族组成。细胞色素P450家族1（CYP1s）在药物和化学致癌物的代谢中起独特作用。在最近的几十年中，已经使用计算方法对这些血蛋白进行了深入的研究，这些计算方法最近得到了显着发展，可通过虚拟筛选化合物以用于药物设计过程中，从而找到具有所需特性的药物。而且，蛋白质和配体对接至其活性位点的分子模型提供了对酶作用机制的深入了解，并使我们能够预测药物代谢的位点。该综述介绍了有关在CYP1s的配体-酶相互作用研究中使用计算方法的知识的现状。从癌症的化学预防，化学疗法和药物相互作用的观点出发，对CYP1s的底物和抑制剂的代谢及其作用选择性的研究特别有价值。