jp507027t_si_001.pdf (3.75 MB)
Dynamics of Lipids, Cholesterol, and Transmembrane α‑Helices from Microsecond Molecular Dynamics Simulations
journal contribution
posted on 2015-12-17, 06:04 authored by Michelle
K. Baker, Cameron F. AbramsExtensive all-atom molecular dynamics
(∼24 μs total)
allowed exploration of configurational space and calculation of lateral
diffusion coefficients of the components of a protein-embedded, cholesterol-containing
model bilayer. The three model membranes are composed of an ∼50/50
(by mole) dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayer
and contained an α-helical transmembrane protein (HIV-1 gp41
TM). Despite the high concentration of cholesterol, normal Brownian
motion was observed and the calculated diffusion coefficients (on
the order of 10–9 cm2/s) are consistent
with experiments. Diffusion is sensitive to a variety of parameters,
and a temperature difference of ∼4 K from thermostat artifacts
resulted in 2–10-fold differences in diffusion coefficients
and significant differences in lipid order, membrane thickness, and
unit cell area. Also, the specific peptide sequence likely underlies
the consistently observed faster diffusion in one leaflet. Although
the simulations here present molecular dynamics (MD) an order of magnitude
longer than those from previous studies, the three systems did not
approach ergodicity. The distributions of cholesterol and DPPC around
the peptides changed on the microsecond time scale, but not significantly
enough to thoroughly explore configurational space. These simulations
support conclusions of other recent microsecond MD in that even longer
time scales are needed for equilibration of model membranes and simulations
of more realistic cellular or viral bilayers.