Colchicine as potential inhibitor targeting MMP-9, NOX2 and TGF-β1 in myocardial infarction: a combination of docking and molecular dynamic simulation study

Abstract

The global data revealed that myocardial infarction (MI) in coronary heart disease has been the leading cause of mortality worldwide in both developing and developed countries. The remodeling process after MI is essential to be the leading cause of heart failure due to cardiac remodeling. The evidence showed the increment of MMP-9, NOX2 and TGF-β1 expressions are biomarkers that influence cardiac remodeling. Lately, colchicine is widely used in the treatment of cardiovascular diseases. The effects of colchicine on NOX2, MMP-9 and TGF-β1 in the molecular models are still not yet discussed. We proposed a molecular docking and molecular dynamics simulation study to show the interaction between colchicine, NOX2, MMP-9 and TGF-β1. Colchicine has a good binding affinity with MMP-9, NOX2 and TGF-β1 based on the value, which are −8.3 Kcal/mol, −6.7 Kcal/mol and −6.5 Kcal/mol, respectively. Colchicine also binds to some catalytic residues in MMP-9, NOX2 and TGF-β1 that are responsible for inhibitor effects. The RMSD values between colchicine and MMP-9, NOX2 and TGF-β1 are 2.4 Å, 2 Å and 2.1 Å, respectively. The RMSF values of ligand and receptors complex showed relatively similar fluctuations. The SASA analysis showed that colchicine could create a more stable interaction with MMP-9. PCA analysis revealed that colchicine is capable of creating a solid and stable interaction with MMP-9 mainly, also NOX2 and TGF-β1. In conclusion, docking and molecular dynamics analysis showed evidence of colchicine roles in the inhibition of MMP-9, NOX2 and TGF-β1 in order to inhibit the remodeling process after MI. Communicated by Ramaswamy H. Sarma