3D QSAR studies on ketoamides of human cathepsin K inhibitors based on two different alignment methods

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 64 ketoamides as human cathepsin K (CatK) inhibitors, using ROCS ligand-based alignment and receptor-based alignment. Results generated from the ligand-based model were found to be superior to those obtained by the receptor-based model. CoMFA and CoMSIA field distributions are in good agreement with the structural characteristics of the binding groove of CatK, suggesting moderate substitutes at the P1, P2, P3 and P1′ may favor the inhibitory activity of ketoamides. These results provide useful information in understanding the structural and chemical features of CatK in designing and finding novel potential CatK inhibitors as osteoporosis therapeutic agents.

Graphical abstractCoMFA and CoMSIA were performed on 64 ketoamides as human cathepsin K inhibitors, using two different alignments. The rcv2 of CoMFA and CoMSIA were 0.663, 0.710 (ligand-based) and 0.640, 0.662 (receptor-based), respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide