Physical properties of mixed membranes explored using atomistic and coarse grained molecular dynamic simulations with enhanced sampling techniques

Abstract

Studies of three different, but interlinked, aspects of membrane properties are presented here. First an analysis of both the lyotropic and thermotropic phase transitions of a phospholipid bilayer using the ELBA1.0 forcefield. This is believed to be the first time such transitions (including the rippled gel phase) have been observed using a coarse grained (CG) forcefield not specifically parameterised to do so. Further, analysis via enhanced sampling methods of the relative free energies of the phases is presented. These analyses confirm the enormous effects comparatively small changes to a forcefield can have on the aggregate behaviour of lipids modelled with it. Molecular dynamics studies on the bending rigidity of bilayers are also presented, including a comparison of 4 different computational methods for calculating the bending rigidity of bilayers. The system size dependency of such methods is compared, as well as their ability to reproduce trends in bending rigidity across lipid species already measured experimentally. The methods are compared across two different atomistic and one CG method for the first time and, despite quite different theoretical bases, are shown to produce surprisingly consistent results both with each other and with previously published experiment.
Finally, two new parameterisations of cholesterol using the ELBA forcefield are explored. Their ability to induce the ordering and structure seen in atomistic simulations is measured and compared with another widely using coarse grained forcefield. ELBA's unique (amongst CG forcefields) direct compatibility with atomistic forcefields also allowed dual-resolution simulations of binary bilayers to be analysed. Results from such dual-resolution simulations are consistent with those resulting from atomistic simulation.

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Identifiers

ORCID for Jonathan W. Essex: orcid.org/0000-0003-2639-2746

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