Free energy barrier for melittin reorientation from a membrane-bound state to a transmembrane state

TL;DR

This study uses umbrella sampling simulations to calculate the free energy barrier for melittin reorientation from membrane surface to transmembrane, revealing effects of peptide concentration and cooperative interactions.

Contribution

It provides the first detailed molecular-level PMF calculations for melittin reorientation, highlighting the influence of peptide ratio and neighboring peptides on the energy barrier.

Findings

Free energy barrier decreases with higher peptide-to-lipid ratio.

Presence of a neighboring transmembrane melittin reduces the reorientation barrier.

Cooperative effects facilitate peptide reorientation in membrane systems.

Abstract

An important step in a phospholipid membrane pore formation by melittin antimicrobial peptide is a reorientation of the peptide from a surface into a transmembrane conformation. In this work we perform umbrella sampling simulations to calculate the potential of mean force (PMF) for the reorientation of melittin from a surface-bound state to a transmembrane state and provide a molecular level insight into understanding peptide and lipid properties that influence the existence of the free energy barrier. The PMFs were calculated for a peptide to lipid (P/L) ratio of 1/128 and 4/128. We observe that the free energy barrier is reduced when the P/L ratio increased. In addition, we study the cooperative effect; specifically we investigate if the barrier is smaller for a second melittin reorientation, given that another neighboring melittin was already in the transmembrane state. We observe that indeed the barrier of the PMF curve is reduced in this case, thus confirming the presence of a cooperative effect.