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目的利用分子对接方法从人体内7种重要的P450酶筛选出与鹿角缩酮B亲和力强的药物代谢酶。方法通过SYBYL-X 2.0软件系统对鹿角缩酮B和7种CYP450酶进行模拟对接评价,按照对接打分分数的高低预测鹿角缩酮B-CYP450蛋白的亲和度;分析人类4种重要CYP450亚型与鹿角缩酮B的对接结果。结果对接打分表明CYP3A4、CYP11B2、CYP2D6、CYP2C9四种酶得到了3分以上的分数,预示酶与鹿角缩酮B二者空间结构上的互补性较高,而CYP1A2、CYP2E1和CYP2A6分数为负分,提示两者空间结合差。预测了人类4种重要CYP450亚型的活性位点,得到了4种重要CYP450亚型与鹿角缩酮B的作用模型的理论信息。结论鹿角缩酮B与CYP3A4的结合最牢固,与CYP2D6的结合较牢固并结合于酶的活性位点,故选择CYP3A4与CYP2D6为进一步的研究提供依据。
OBJECTIVE: To screen out the drug-metabolizing enzymes with high affinity to antler Ketone B from seven important P450 enzymes in the human body by molecular docking. Methods The anthem ketal B and 7 kinds of CYP450 enzymes were evaluated by SYBYL-X 2.0 software system, and the affinities of antler ketal B-CYP450 protein were predicted according to the docking score. The four major CYP450 subtypes Butane ketal B and docking results. The results showed that the docking scores of CYP3A4, CYP11B2, CYP2D6, CYP2C9 four enzymes were scored more than 3 points, indicating that the enzyme and antler ketal B both spatial structure of the higher complementarity, and CYP1A2, CYP2E1 and CYP2A6 score negative , Suggesting that the two space combination of poor. The active sites of four important CYP450 subtypes were predicted, and theoretical information on the action models of the four important CYP450 subtypes and antler ketal B was obtained. Conclusion Antagonistic ketal B binds with CYP3A4 the most firmly, and binds strongly with CYP2D6 and binds to the active site of the enzyme. Therefore, the choice of CYP3A4 and CYP2D6 provide the basis for further study.