Thermodynamic Analysis of Protegrin-1 insertion and Permeation through a Lipid Bilayer

Abstract

The molecular dynamics (MD) simulations are used to study the pathway for the insertion of the cationic antimicrobial peptide protegrin-1, (PG1) into anionic POPG and neutral POPE lipid bilayers at 310 K. We calculate the potential of mean force (PMF) during transfer of protein from the bulk of aqueous phase to the transmembrane (TM) configuration using the the adaptive-biasing-force method which is implemented as a part of the collective Variables Module of NAMD. We find that the PMF has two energy minima and one potential barrier. One minimum corresponds to full insertion TM configuration. The second PMF minimum corresponds for adsorption to the membrane surface. The PMF exposes the existence of the potential barrier for the insertion process.Using Langevin equation for Kramers theory and generalized Langevin equation for Grote-Hynes theory we calculated the transmission coefficient for PG1 diffusion through the potential barrier. We focus on use of the PMF and time correlation function of the fluctuation instantaneous force to calculate the rate constants for insertion of PG1 into the POPG and POPE membranes. The influence of the activation free energy barrier to the dynamic of the insertion and permeation for peptides through the membranes are discussed.