Effect of short antimicrobial peptides on bacterial membranes from coarse-grained molecular dynamics simulations

FRIGINI, EZEQUIEL N; PANTANO, SERGIO; ENRIZ, RICARDO D.; PORASSO, RODOLFO D.

Rosario, Santa Fe

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Antimicrobial peptides (AMPs) are naturally-occurring molecules that exhibit strong antibiotic properties against numerous infectious bacterial strains. Because of their unique mechanism of action, they have been touted as a potential source for novel antibiotic drugs. The AMPs act on cell membranes causing cell lysis or alteration of the membrane topology. In this work, coarse-grained (CG) molecular dynamics simulations of vesicles were carried out in the presence of short AMPs to gain insights into their mode of action.Peptides with different charges (net charge: 0 and +4) were used. The lipids used to build the vesicles are: palmitoyl-oleoyl phosphoethanolamine (POPE) and palmitoyl-oleoyl phosphatidylglycerol (POPG, parametrized in this work) with a contains of 80/20 %, respectively. The CG force field SIRAH 2.0 was used to carry out the simulations. This force field has parameters for amino acids, ions, lipids and two water models that represent the solvent at the CG and supraCG resolution named WatFour (WT4) and WatElse (WLS), respectively. A dual-resolution solvation scheme was used with the WT4 and WLS water models.Analyzes of MD simulations in terms of area per lipid, thickness of the bilayer, volume per lipid, sphericity and roundness of the vesicle, the curvature order parameter, and peptidelipid interactions produced a remarkable agreement with previously published biophysical data. The results indicate that the peptides without and with charges are adsorbed differentially on the surface of the vesicle due to the presence of TRP. The neutral peptides only alter the properties on the outer lipid leaflet, leaving the global topology of the vesicle intact. In contrast, charged peptides destabilize the membrane causing drastic changes in the whole vesicle topology