Background: Matrix metalloproteinase 1 are zinc-dependent endopeptidases responsible
for the controlled breakdown of the extracellular matrix resulting in the maintenance of
homeostasis. Dysregulation of MMP1 leads to the progression of various pathological conditions
like cancer, rheumatoid arthritis, cardiovascular disease, skin damage and fibrotic disorder. Thus,
MMP1 inhibition is the potential drug target of many synthetic MMP1 inhibitors but lack of
substrate specificity hinders their clinical applicability. Hence, inhibitors from natural products
have gained widespread attention.
Objective: The present study attempts screening of novel MMP1 inhibitors from the ZINC
database based on experimentally reported natural inhibitors of MMP1 as a scaffold.
Methods: Molecular docking study was performed with 19 experimentally reported natural
inhibitors spanning across nine different classes followed by virtual screening using the selected
compounds. The selected compounds were subjected to molecular dynamics simulation.
Results: Twenty compounds were screened with a cut-off of -9.0 kcal/mol of predicted free energy
of binding, which further converged to 6 hits after docking studies. After comparing the docking
result of 6 screened hits, two best compounds were selected. ZINC02436922 had the best
interaction with six hydrogen bond formation to a relatively confined region in the S1’site of
MMP1 and -10.01 kcal/mol of predicted free energy of binding. ZINC03075557 was the secondbest
compound with -9.57 kcal/mol predicted binding free energy. Molecular dynamics simulation
of ZINC02436922 and ZINC03075557 corroborates docking study.
Conclusion: This study indicated phenolic compounds ZINC02436922 and ZINC03075557 as
potential MMP1 inhibitors.