Li Yong-Liang, Du Zhi-Yun, Zheng Jie
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510000, China.
Institute of Natural Medicine and Green Chemistry, Guangdong University of Technology, Guangzhou 510000, China.
Zhongguo Zhong Yao Za Zhi. 2017 May;42(10):1951-1956. doi: 10.19540/j.cnki.cjcmm.2017.0083.
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 pIC₅₀on MEK1 inhibitors, with R²=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.
MEK1（丝裂原活化蛋白激酶激酶1）的过度磷酸化是黑色素瘤的病因之一。通过对中药化学成分针对MEK1进行虚拟筛选来发现一种潜在的黑色素瘤药物具有重要意义。在本研究中，利用MEK1晶体结构构建了对接口袋模型和柔性搜索模型，晶体结构中连接体构象与配子体构象之间的相似度为0.784。MEK1抑制剂的总分与pIC₅₀之间存在线性关系，R² = 0.937，这进一步表明了虚拟筛选模型的可靠性。将符合Lipinski规则的中药数据库搜索库与口袋模型进行对接，然后通过柔性模型获得了50个总分超过7.0的化合物。本文筛选结果中排名前10的活性成分的总分高于阳性药物。有望进一步研究其对MEK1和黑色素瘤的抑制作用。
