Insights into the inhibitory mechanism of rimantadine drug against p7 viroporin by molecular dynamic simulation

Viral channels can change membrane permeability, disturb the cations balance in host cells, upset the ionic flux across target membranes and, thus they can change physiological cell functions and induce cell death[1-3]. In the present work, the set computational studies was performed to get insights into molecular details understanding of a rimantadine binding site. Also, the MMPBSA method was used to evaluate the binding free energy and decomposing free energy per residue. Binding free energy analysis revealed that the hydrophobic residues had the major contribution in the binding of drug and formed the strongest hydrophobic bond with drug. According to the MD analyzing and the energy profiles, the hydrophobic connections were the main driving force for drug binding. In particular, this work has tried to investigate the mechanism by which rimantadine inhibits the activity of p7 channel of hepatitis C virus using methods like molecular docking, MD simulation, and binding free energy calculation. our results revealed that inhibitor binding to hydrophobic pocket can block channel activity by restricting significant intrinsic channel breath at the restriction region of the channel.

کلیدواژه ها:

viroporin ، binding free energy ، P7 ، MMPBSA ، molecular dynamic simulation