基于分子对接虚拟筛选MEK1中药抑制活性成分  

Docking-based virtual screening of MEK1 inhibitors from Chinese herbs

作　　者：黎永良[1,2] 杜志云[1,2] 郑杰[1,2] 

机构地区：[1]广东工业大学轻工化工学院,广东广州510000 [2]广东工业大学天然药物与绿色化学研究所,广东广州510000

出　　处：《中国中药杂志》2017年第10期1951-1956,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(21272043);广东省药食同源资源综合利用工程技术中心(15ZK0213)

摘　　要：有丝分裂原活化蛋白激酶激酶1(mitogen-activated protein kinase kinase,MEK1)的过度磷酸化是黑色素瘤成因之一,基于该靶点的中药成分虚拟筛选有望发现中药在治疗黑色素瘤潜在应用价值。采用MEK1晶体构象构建口袋模型和Flex Search模型,模型可很好重现晶体结构,对接配体构象与晶体结构中原配体构象similarity评分为0.784;对接评分与已有MEK1抑制剂活性数据pIC_(50)呈线性关系,R^2=0.937,进一步表明虚拟筛选模型可靠。以口袋模型对Lipinski五规则初筛的中药成分库进行分子对接,根据Flex Search模型精筛,最终得到50个总分高于7.0的化合物,该研究给出总分高于阳性对照的前10个中药成分,有望进一步用于MEK1和黑色素瘤抑制的研究。The hyperphosphorylation of MEK1（mitogen-activated protein kinase kinase 1） is one of the causesfor melanoma. It is important to discover a potential medicine for melanoma through virtual screening of chemical composition of Chinese material medica on MEK1. In this study, a docking pocket model and Flex Search model were built by using a MEK1 crystal structure, the similarity between connector conformation and gametophyte conformation in the crystal structure was 0.784.There was a linear relationship between total score and pIC50 on MEK1 inhibitors, with R^2=0.937, which further indicated the reliability of the virtual screening model.The search library of traditional Chinese medicine database on the Lipinski＇s rule was docked with the pocket model, and then 50 compounds with a totalscore of more than 7.0 were obtained by the Flex model. In this paper, top 10 active ingredients in screening results showed atotal score of more than that of positive medicines. It is expected to further research the inhibition of MEK1 and melanoma.

关 键 词：MEK1抑制剂 中药成分 分子对接 虚拟筛选 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学]