Spontaneous curvature generation by peptides in asymmetric bilayers.

Peptides and proteins play crucial roles in membrane remodeling by inducing spontaneous curvature. However, extracting spontaneous curvatures from simulations of asymmetric bilayers is challenging because differential stress (i.e., the difference of the leaflet surface tensions) arising from leaflet area strains can vary substantially among initial conditions. This study investigates peptide-induced spontaneous curvature δc 0 p $$ {\delta c}_0^{\mathrm{p}} $$ in asymmetric bilayers consisting of a single lipid type and a peptide confined to one leaflet; δc 0 p $$ {\delta c}_0^{\mathrm{p}} $$ is calculated from the Helfrich equation using the first moment of the lateral pressure tensor and an alternative expression using the differential stress. It is shown that differential stress introduced during initial system generation is effectively relaxed by equilibrating using P2 1 periodic boundary conditions, which allows lipids to switch leaflets across cell boundaries and equalize their chemical potentials across leaflets. This procedure leads to robust estimates of δc 0 p $$ {\delta c}_0^{\mathrm{p}} $$ for the systems simulated, and is recommended when equality of chemical potentials between the leaflets is a primary consideration.