Molecular dynamics study of the solution behaviour of antimicrobial peptide indolicidin

Abstract

Understanding the mechanism of action of antimicrobial peptides (AMPs) on bacterial cells requires detailed knowledge of how AMPs interact with bacterial membranes. Our hypothesis is that the peptides do not interact with the membrane as monomers, but rather form clusters, that collectively approach the cell and attack the membrane. In this paper we investigate the behavior of the antimicrobial peptide indolicidin in solution, prior to their interaction with the bacterial membrane, by means of coarse grain molecular dynamics simulations (CG-MD). We show that indolicidin in particular and, probably, charged linear AMPs in general tend to aggregate in solution, forming globular amphipathic clusters with a central hydrophobic core. The dependence of the clusters size on the peptide concentration and on the temperature is studied, as well as the influence of the finite size of the simulation box. Our results manifest the investigation of the AMPs behavior in solution prior to membrane impact as an indispensable element in revealing the mechanism of their antimicrobial activity.