CoMFA 3D-QSAR Analysis of Epothilones Based on Docking Conformation and Alignment

Epothilones belong to a class of novel microtubule stabilizing and anti‐mitotic agents, which have a paclitaxel‐like mechanism of action. A three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) model was built for epothilones by the method of comparative molecular field analysis (CoMFA) combined with the flexible docking technology. The docking CoMFA model gave a good cross‐validated value of q²=0.784 with an optimized component of 6 and the conventional correlation coefficient of r²=0.985. The statistical results show that the model has good ability to predict the activity of the studied compounds. At last, the docking CoMFA model was analyzed through contour maps complemented with MOLCAD‐generated active site potential surface in the α,β‐tubulin receptor, which can provide important information for the structure‐based drug design.