鹿角缩酮B与人CYP450主要亚型的对接研究

Docking Studies on Xyloketal B with Human Major CYP450 Isoforms

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 the strong affinity drug metabolic enzymes of Xyloketal B with 7 human major CYP450 isoforms by molecular docking method. METHODS By SYBYL-X 2.0 software system,Xyloketal B were docked with 7 human major CYP450 isoforms to predicate the affinity of Xyloketal B-CYP450 enzymes according to the docking total score. Analyze the docking results of Xyloketal B with 4 major CYP450 isoforms. RESULTS The docking total score of Xyloketal B with CYP3A4,CYP11B2,CYP2D6,CYP2C9 was more than 3,that predicted the more structural complementarity of Xyloketal B with the 4 drug metabolic enzymes. The docking total score of Xyloketal B with CYP1A2,CYP2E1,CYP2A6 was negative points,that predicted the lower space combination of Xyloketal B-enzymes. The activity sites of 4 human major CYP450 isoforms with Xyloketal B were predicated and the theory of the model of Xyloketal B with 4 human major CYP450 isoforms were acquired. CONCLUSION Xyloketal B-CYP3A4 was the strongest combination. Xyloketal B-CYP2D6 was the stronger combination and the combination was with the enzyme active site. So CYP3A4 and CYP2D6 were chosen for the further research.