A cheminformatics-biophysics correlate to identify promising lead molecules against matrix metalloproteinase-2 (MMP-2) enzyme: A promising anti-cancer target

Matrix metalloproteinase-2 (MMP-2) is an endopeptidase enzyme that is devoted to extracellular matrix proteins degradation. The enzyme is warranted as promising drugs target for different light threating diseases such as arthritis, cancer and fibrosis. Herein, in this study, three drug molecules: CMNPD8322, CMNPD8320, and CMNPD8318 were filtered as high affinity binding compounds with binding energy score of −9.75 kcal/mol, −9.11 kcal/mol, −9.05 kcal/mol, respectively. The control binding energy score was −9.01 kcal/mol. The compounds docked deeply inside the pocket interacting with S1 pocket residues. The docked complexes dynamics in real time at cellular environment was then done to decipher the stable binding conformation and intermolecular interactions network. The compounds complexes achieved very stable dynamics with root mean square deviation (RMSD) with mean value of around 2–3 Å compared to control complex that showed higher fluctuations of 5 Å. The simulation trajectories frames based binding free energy demonstrated all the compounds-MMP-2 complexes reported highly stable energy, particularly the van der Waals energy dominate the overall net energy. Similarly, the complexes revalidation of WaterSwap based energies also disclosed the complexes highly stable in term docked conformation. Also, the compounds illustrated the compounds favorable pharmacokinetics and were non-toxic and non-mutagenic. Thus, the compounds might be used thorough experimental assays to confirm compounds selective biological potency against MMP-2 enzyme.