Modeling the Ligand−Receptor Interaction for a Series of Inhibitors of the Capsid Protein of Enterovirus 71 Using Several Three-Dimensional Quantitative Structure−Activity Relationship Techniques

The structure of enterovirus 71 (EV71) capsid protein VP1 has been constructed by using homology modeling and molecular dynamics simulation techniques. The ligand structures were a series of EV71 VP1 inhibitors synthesized by Shia et al. in 2002 and Chern et al. in 2004. The training set was selected by the VOLSURF4.1/PCA program and the IC50 values varied from 0.06 to 10.83 microm. Then, the training set was analyzed by the following three-dimensional quantitative structure-activity relationship techniques: CoMFA, CoMSIA, CATALYST4.9, and VOLSURF4.1/PCA. The model generated by a two-stage flexible docking procedure and without any structural alignment has far more significant statistics. Highly accurate activities for the test sets were then predicted by the top hypothesis of the CATALYST program and were compared with those predicted by CoMFA, CoMSIA, and VOLSURF. These studies identified some important clues for searching or making more potent inhibitors against the EV71 infection.