Coarse-grained model of titrating peptides interacting with lipid bilayers.

Molecular-level computer simulations of peptide aggregation, translocation, and protonation at and in biomembranes are impeded by the large time and length scales involved. We present a computationally efficient, coarse-grained, and solvent-free model for the interaction between lipid bilayers and peptides. The model combines an accurate description of mechanical membrane properties with a new granular representation of the dielectric mismatch between lipids and the aqueous phase. All-atom force fields can be easily mapped onto the coarse-grained model, and parameters for coarse-grained monopeptides accurately extrapolate to membrane permeation free energies for the corresponding dipeptides and tripeptides. Acid-base equilibria of titratable amino acid residues are further studied using a constant-pH ensemble, capturing protonation state changes upon membrane translocation. Important differences between histidine, lysine, and arginine are observed, which are in good agreement with experimental observations.