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细胞色素酶P450是人体内重要的药物代谢酶.通常,这类酶在其结构中都含有一个亚铁血红色分子,并且负责代谢超过90%的已知药物分子.细胞色素酶2D6是这类酶中的重要一员,它负责代谢大约20%～30%的已知药物分子.利用分子对接和分子动力学模拟的方法,研究了细胞色素酶2D6的结构特征以及其与药物分子之间的相互作用.并且发现,细胞色素酶2D6活性位点中的Glu216,Asp301,Ser304和Ala305在其与药物分子的相互作用中有着重要的作用.它们可以形成一个或者多个氢键来固定药物分子.同时其活性位点中的Phe120可以通过形成一定的Π-Π相互作用来识别和固定药物分子.这些发现有助于进一步了解细胞色素酶2D6的结构特征,特别是其活性位点附近的结构特征,理解细胞色素酶2D6代谢药物的机理.同时,由于细胞色素酶2D6存在着单核苷酸多肽性,所得到的结果可以为个性化医疗提供一定的理论基础.
Cytochrome P450 is an important drug-metabolizing enzyme in the human body.Usually, these enzymes contain a ferrous red molecule in their structure and are responsible for metabolizing more than 90% of known drug molecules.Cytochrome 2D6 is the Which is responsible for the metabolism of about 20% to 30% of the known drug molecules.Using molecular docking and molecular dynamics simulation method, the structural characteristics of the cytochrome enzyme 2D6 and its interaction with drug molecules And found that Glu216, Asp301, Ser304 and Ala305 in the active site of cytosolic 2D6 play an important role in their interaction with drug molecules, and they can form one or more hydrogen bonds to immobilize Drug molecules, and Phe120 in its active site can identify and fix the drug molecules through the formation of certain Π-Π interactions.These findings help to further understand the structural features of cytosolic 2D6, especially its active site Near the structural features, understand the mechanism of cytochromes 2D6 metabolism drugs at the same time, due to the existence of single nucleotide polymorphism of cytochrome dihydrogenase 2D6, the results can be provided for personalized medical Set the theoretical basis.