Computational Simulation of a Beta-helical Tubular Peptide in a Lipid Bilayer

Abstract

Peptides having a regularly repeating pattern of L and D amino acids adopt unique structures termed beta-helix. In beta helix structure, intramolecular hydrogen bonding looks like that in parallel β-sheets. The beta helix structure has been reported for both natural peptides, like gramicidin A, and syntetic peptides such as poly (D, L-γ -benzylglutamyl). Studies have shown a short beta sheet tetraicosa-peptide (VSLGLSIAFSVAVSIAWSFARSRG, where all As are D-alanine) accept beta-helical conformation in lipid bilayer similar to gramicidin A [4], called gramicidin-like channel (GLC).In the present work, the GLC syntetic peptide has been modeled and simulated in different orientations with respect to a lipid bilayer. The aim of this study was to find the stable conformation of the peptide and understanding its key interactions with lipid bilayer. GROMOS force field implemented in GROMACS software, version 4.0 was employed for the molecular dynamics simulations. The results showed that this peptide adopted beta helical structure, in agreement with the previous studies. However, GLC was stable in the trans-membrane state during 20 ns molecular dynamics simulation. The findings of this study proved that the elctrostatic interactions between the polar residues of the peptide and the polar head group of the lipid bilayer are the most important interactions in the insertion of peptide into the membrane. Furthermore, simulation revealed that the hydrophobic interactions play a key role in the stability of GLC peptide in hydrophobic environment of lipid bilayer.