作用于秋水仙碱结合位点的微管蛋白抑制剂药效团的构建

目的:构建作用于秋水仙碱结合位点的微管蛋白抑制剂药效团模型;初步分析该类抑制剂与靶点的作用方式。方法:使用Discovery Studio软件中的HypoGen模块对训练集进行药效团模型的构建。结果:最佳药效团模型的线性回归相关系数最高(0.981),包含1个氢键给体和4个疏水中心,利用测试集验证了该药效团模型的活性预测能力;通过分子与活性位点的对接得到了活性最好的两个化合物与此结合位点的具体作用方式。结论:得到的药效团模型具有较好的预测能力,有利于设计和开发新型微管蛋白抑制剂。

Development and validation of pharmacophore model of tubulin inhibitors which bind to the colchicine-site

Objective:To develop a pharmacophore model of tubulin inhibitors which bind to the colchicine-site and preliminarily elucidate how this kind of inhibitors interact with the active site.Methods:The pharmacophore models were developed based on the training set by using HypoGen module in Discovery Studio.Results:The best pharmacophore model,which has the highest linear regression correlation coefficient(0.981),consists of one hydrogen-bond donor and four hydrophobic features.The pharmacophore model was further validated by test set.Through molecular docking with the active site we found the way how those two compounds,with the best activity,interact with the colchicine-site.Conclusion:The established pharmacophore model has good predictive ability and can be further used to develop novel tubulin inhibitors.