prediction and interaction of resveratrol on methyl-CpG binding proteins by molecular docking and MD simulations study.

Abstract

Resveratrol is known to upregulate BRCA1 gene expression, while methyl-CpG binding domain (MBD) proteins associate with the BRCA1 promoter region. This computational study examined the binding characteristics of resveratrol with MBD1, MBD2, and MeCP2 proteins. Molecular docking revealed the strongest affinity for MeCP2 (ΔG = -6.5), involving four hydrogen bonds. Molecular dynamics simulations demonstrated stabilization of all three protein–ligand complexes beyond 75 ns, with backbone RMSD fluctuations of 0.4 Å, 0.5 Å, and 0.7 Å for MBD1, MBD2, and MeCP2, respectively. Binding free energy calculations yielded values of -94.764, -53.826, and -36.735 kJ/mol for MeCP2-, MBD2-, and MBD1-resveratrol complexes, corroborating the docking outcomes. The findings also indicate that MBD family proteins interact with signaling partners implicated in cancer initiation pathways.

Mechanism

Resveratrol forms four hydrogen bonds with MeCP2, yielding the most stable complex (binding free energy -94.764 kJ/mol) among MBD family members, potentially modulating BRCA1 promoter regulation through competitive or allosteric interference with MBD protein binding.