  Lipid bilayers composed of non-alpha hydroxy sphingosine ceramide (CER NS),
cholesterol (CHOL), and free fatty acids (FFA), which are components of the
human skin barrier, are studied via molecular dynamics simulations. Since
mixtures of these lipids exist in dense gel phases with little molecular
mobility at physiological conditions, care must be taken to ensure that the
simulations become decorrelated from the initial conditions. Thus, we propose
and validate an equilibration protocol based on simulated tempering in which
the simulation takes a random walk through temperature space, allowing the
system to break out of metastable configurations and hence become decorrelated
form its initial configuration. After validating the equilibration protocol,
the effects of the lipid composition and ceramide tail length on bilayer
properties are studied. Systems containing pure CER NS, CER NS + CHOL, and CER
NS + CHOL + FFA, with the CER fatty acid tail length varied within each CER
NS-CHOL-FFA composition, are simulated. The bilayer thickness is found to
depend on the structure of the center of the bilayer, which arises as a result
of the tail length asymmetry between the lipids studied. The hydrogen bonding
between the lipid headgroups and with water is found to change with the overall
lipid composition, but is mostly independent of the CER fatty acid tail length.
Subtle differences in the lateral packing of the lipid tails are also found as
a function of CER tail length. Overall, these results provide insight into the
experimentally observed trend of altered barrier properties in skin systems
where there are more ceramides with shorter tails present.
