3D-QSAR, molecular docking and molecular dynamics studies of a series of RORγt inhibitors

In the present work, to find out the structural features required for the inhibitory activity, we show for the first time a three-dimensional quantitative structure–activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations for a series of novel thiazole/thiophene ketone amides with inhibitory activity at the RORγt receptor.

The optimum CoMFA and CoMSIA models, derived from ligand-based superimposition I, exhibit leave-one-out cross-validated correlation coefficient ( R 2 cv ) of .859 and .805, respectively. Furthermore, the external predictive abilities of the models were evaluated by a test set, producing the predicted correlation coefficient ( R 2 pred ) of .7317 and .7097, respectively. In addition, molecular docking analysis was applied to explore the binding modes between the inhibitors and the receptor.