Protein-based Alignment in 3D-QSAR of Polo-Like Kinase 4 Inhibitors

Abstract

Polo-like kinase 4 (PLK4), a mitotic kinase was regarded as a potential target for cancer therapy. Three-dimensional quantitative structure–activity relationship (3D QSAR) studies were performed on PLK4 inhibitors, based on molecular docking obtained by using GOLD and comparative molecular field analysis (CoMFA). The high leave one out (LOO) cross-validated correlation coefficient (q2 = 0.531) reveals that the model is a useful tool for the prediction of test set as well as newly designed structures against PLK4 activity. The superimposed CoMFA models on the receptor site of PLK4 are guiding the design of potential inhibitory structures directed against PLK4 activity.