Interaction of antibacterial CM11 peptide with the gram-positive and gram-negative bacterial membrane models: a molecular dynamics simulations study

In the present study, a series of all-atom molecular dynamics simulations were applied to shed light on the molecular mechanism of the activity of CM11, a short cecropin–melittin hybrid peptide obtained through a sequence combination approach, against Gram-positive (GP) and Gram-negative (GN) bacterial membrane models. In addition, the peptide adsorption mechanism on the surface of the membrane models, the thermodynamic and structural contribution of each residue in the antibacterial activity of the peptide against both GP and GN bacterial membranes were investigated. Our findings showed that the peptide was strongly bound to the GP membrane type in comparison with the GN membrane and was stabilized quickly. These strong bonds are caused by the interactions between basic residues and POPG molecules, which have higher concentrations in GP than GN membranes. Calculation of binding free energies revealed that both electrostatic and van der Waals energy components were desired for the peptide binding and insertion in the membrane. Electrostatic interactions were the main driving force in the adsorption and surface localization of the peptide. Determining the contribution of each residue to the binding free energy indicated that W1, K2, K5, K6 and K9 residues played an important role in the activity of the peptide. These results can be used as a roadmap to provide in-depth insights into the design of appropriate peptides in the fight against multidrug-resistant bacteria.