Computational Investigations of Pore Forming Peptide Assemblies in Lipid Bilayers

Abstract

This Letter presents the first application of a three-dimensional numerical molecular theory based modeling approach to study the structure and energetics of assemblies of peptides embedded in lipid bilayers. Coarse-grained models were used for both the peptides and lipids. Both barrel-stave and toroidal pore morphologies for the lipids near the peptide assemblies are found, but at different assembly sizes. The free energy of the assembly is found to have a global free energy minimum for a solution with a membrane-spanning toroidal pore. A pairwise approximation to this free energy is found to underpredict the free energy minimum associated with the membrane-spanning pores.

Mesoscopic Membrane Physics: Concepts, Simulations, and Selected Applications

“…Since the generally positively charged antimicrobial peptides experience an electrostatic repulsion, one might expect them to prefer the toroidal morphology in nature, as seems to be borne out by experimental observations. [104] Frink and Frischknecht [105] have investigated the same balance recently using a density functional theory and, for the system studied, found the toroidal pore to be the more stable arrangement.…”

Computer Simulation of Antimicrobial Peptides

“…This time scale will become easier to reach as computers get faster. Recent developments on coarse-grained models of lipids and peptides also show promise for large scale simulations involving many peptides as well as lipid mixtures [147][148][149] although there are issues with the accurate representation of water defects (at the limits of the resolution of a semi-atomistic model) and the accuracy of very specific interactions such as the details of hydrogen bonding, if these turn out to be important.…”

Chapter 5 Implicit Modeling of Membranes

“…Although the details of their formulation are too complex to describe here, it is interesting to note that once again the lateral pressure profile plays a central role. They have applied their model to explore the effects of alcohols on lipid structure (Frischknecht and Frink, 2006), and to explore poreformation due to the binding of rigid helices (Frink and Frischknecht, 2006). By contrast to the models described in Section II.A, their model allowed them to compare different modes of pore-formation.…”