An Extension and Further Validation of an All-Atomistic Force Field for Biological Membranes

Biological membranes are versatile in composition and
host intriguing
molecular processes. In order to be able to study these systems, an
accurate model Hamiltonian or force field (FF) is a necessity. Here,
we report the results of our extension of earlier developed all-atomistic
FF parameters for fully saturated phospholipids that complements an
earlier parameter set for saturated phosphatidylcholine lipids (J. Phys. Chem. B, 2012, 116, 3164–3179). The FF, coined Slipids (Stockholm lipids), now
also includes parameters for unsaturated phosphatidylcholine and phosphatidylethanolamine
lipids, e.g., POPC, DOPC, SOPC, POPE, and DOPE. As the extended set
of parameters is derived with the same philosophy as previously applied,
the resulting FF has been developed in a fully consistent manner.
The capabilities of Slipids are demonstrated by performing long simulations
without applying any surface tension and using the correct isothermal–isobaric
(NPT) ensemble for a range of temperatures and carefully
comparing a number of properties with experimental findings. Results
show that several structural properties are very well reproduced,
such as scattering form factors, NMR order parameters, thicknesses,
and area per lipid. Thermal dependencies of different thicknesses
and area per lipid are reproduced as well. Lipid diffusion is systematically
slightly underestimated, whereas the normalized lipid diffusion follows
the experimental trends. This is believed to be due to the lack of
collective movement in the relatively small bilayer patches used.
Furthermore, the compatibility with amino acid FFs from the AMBER
family is tested in explicit transmembrane complexes of the WALP23
peptide with DLPC and DOPC bilayers, and this shows that Slipids can
be used to study more complex and biologically relevant systems.