Effect of Peptide Sequence Mutations on the Translocation of Charged Peptide Loops across Lipid Bilayers with Molecular Dynamics Simulations

Abstract

The hydrophobic core of the cell membrane is considered largely impermeable to charged molecules because of the large free energy barrier and corresponding long timescale (∼hours) for charge translocation. Contradicting this view, a variety of water-soluble peptides are known to translocate charged groups across the cell membrane on a surprisingly rapid ∼seconds timescale, for at least some peptides. In this work, we study the interconversion of single α-helix peptides with charged flanking loops between a surface-adsorbed and membrane-embedded state, which requires the translocation (or “flipping”) of charged loops across the bilayer.