Coarse-grained model of titrating peptides interacting with lipid bilayers

Summary, in English

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.

• Author: Giulio Tesei; Mario Vazdar; Mikael Lund
• Department/s: Computational Chemistry; eSSENCE: The e-Science Collaboration
• Publishing year: 2018
• Language: English
• Publication/Series: The Journal of chemical physics
• Volume: 149
• Issue: 24
• Links: http://dx.doi.org/10.1063/1.5058234
• Document type: Journal article
• Publisher: American Institute of Physics (AIP)
• Topic: Physical Chemistry (including Surface- and Colloid Chemistry)
• Status: Published
• ISBN/ISSN/Other: ISSN: 0021-9606