Impact of the subtle differences in MMP-12 structure on Glide-based molecular docking for pose prediction of inhibitors

• Glide-based cross-docking can be used to access subtle differences in MMP-12 (Matrix metalloproteinase-12) structures.
• Some MMP-12 PDB IDs obtained through Glide-based cross-docking are more suitable for inhibitor pose prediction.
• Many factors from PDB files provide clues for choosing a suitable PDB ID when docking.

Human MMP-12 is involved in many aspects of disease pathology. Substantial efforts have been made to develop MMP-12 inhibitors. However, the mechanism of some MMP-12 inhibitors is still unclear. Recently, the method of molecular modeling was used to explore the mechanism, but selecting the best candidate among the wealth of MMP-12 structures poses a challenge. In this study, we attempted to identify several criteria to predict the most appropriate MMP-12 PDB ID for enzyme–ligand interaction studies based on cross-docking by Glide. Furthermore, the parameters from PDB files such as R-free, resolution, B factor, and the molecular volume of the ligand in the complex can provide useful clues for choosing a suitable approximate initial model for pose prediction for MMP-12 inhibitors. This work might also provide a useful reference for other drug targets.