Inclusion of Lateral Pressure/Curvature Stress Effects in Implicit Membrane Models

Implicit membrane models usually treat the membrane as a hydrophobic slab and neglect lateral pressure/curvature stress effects. As a result, they cannot distinguish, for example, PE from PC lipids. Here, the implicit membrane model IMM1 is extended to include these effects using a combination of classical thermodynamics and membrane elasticity theory. The proposed model is tested by molecular dynamics simulation of the peptides alamethicin, melittin, cyclotide kalata B1, 18A, and KKpL15. The lateral pressure term stabilizes interfacial binding due to the negative pressure at the hydrocarbon-water interface. In agreement with experiment, increase in the peptide/lipid molar ratio shifts the equilibrium from the interfacial to the transmembrane orientation. Simulations of mixed DOPC/DOPE bilayers show that increase of the DOPE mole fraction in general stabilizes interfacial orientations and destabilizes transmembrane orientations. The extent of the stabilization or destabilization varies depending on the exact position of the peptides. The computational results are in good agreement with experiments.