Characterizing Residue-Bilayer Interactions Using Gramicidin A as a Scaffold and Tryptophan Substitutions as Probes Academic Article uri icon

Overview

MeSH Major

  • Elasticity
  • Gramicidin
  • Lipid Bilayers
  • Molecular Dynamics Simulation

abstract

  • Previous experiments have shown that the lifetime of a gramicidin A dimer channel (which forms from two nonconducting monomers) in a lipid bilayer is modulated by mutations of the tryptophan (Trp) residues at the bilayer-water interface. We explore this further using extensive molecular dynamics simulations of various gA dimer and monomer mutants at the Trp positions in phosphatidylcholine bilayers with different tail lengths. gA interactions with the surrounding bilayer are strongly modulated by mutating these Trp residues. There are three principal effects: eliminating residue hydrogen bonding ability (i.e., reducing the channel-monolayer coupling strength) reduces the extent of the bilayer deformation caused by the assembled dimeric channel; a residue's size and geometry affects its orientation, leading to different hydrogen bonding partners; and increasing a residue's hydrophobicity increases the depth of gA monomer insertion relative to the bilayer center, thereby increasing the lipid bending frustration.

publication date

  • October 10, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5634937

Digital Object Identifier (DOI)

  • 10.1021/acs.jctc.7b00400

PubMed ID

  • 28870079

Additional Document Info

start page

  • 5054

end page

  • 5064

volume

  • 13

number

  • 10