Analyzing binding interface of HDAC7-MEF2A interactions using molecular dynamics simulation

Molecular interaction of HDAC7 with MEF2A regulated MEF2A activity. Despite prior investigations on the interaction between these proteins, a detailed investigation leading to identification of key amino acid residues crucial to establish the interprotein complex remains unknown. We used molecular modeling and molecular dynamics (MD) simulations in our investigations and identified the key amino acid residues across the binding interface that are responsible for the formation of HDAC7-MEF2A complex. Our result revealed that the structural stability of the HDAC7-MEF2A complex is mainly mediated through hydrophobic interactions as well as hydrogen bonding between SER82 and LYS96 with ASP63 and salt-bridge formation between LYS96 and ASP63. Our results further suggests that binding of DNA to MEF2A does not significantly alter HDAC7-MEf2A interactions.