Combined 3D-QSAR, molecular docking, and molecular dynamics study on potent cyclohexene-based influenza neuraminidase inhibitors

The activities of a cyclohexene series of influ- enza neuraminidase inhibitors were studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics methods. The 3D-QSAR models were established by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimum CoMFA and CoMSIA models yielded satisfactory statistical results: the leave-one-out cross-validation correlation coefficients (q 2 ) were 0.722 and 0.779, respectively. The corresponding non-cross-validated r 2 were both 0.996. Based on the built 3D-QSAR models, several new neuraminidase inhibitor analogs were designed. Molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket of neuraminidase protein. Molecular dynamics simulation further determined the binding pro- cess and validated the rationality of docking results.