L. Koubi et al., Distribution of halothane in a dipalmitoyl phosphatidylcholine bilayer from molecular dynamics calculations, BIOPHYS J, 78(2), 2000, pp. 800-811
We report a 2-ns constant pressure molecular dynamics simulation of halotha
ne, at a mol fraction of 50%, in the hydrated liquid crystal bilayer phase
of dipalmitoylphosphatidylcholine. Halothane molecules are found to prefere
ntially segregate to the upper part of the lipid acyl chains, with a maximu
m probability near the C-5 methylene groups. However, a finite probability
is also observed along the tail region and across the methyl trough. Over 9
5% of the halothane molecules are located below the lipid carbonyl carbons,
in agreement with photolabeling experiments. Halothane induces lateral exp
ansion and a concomitant contraction in the bilayer thickness. A decrease i
n the acyl chain segment order parameters, S-CD, for the tail portion, and
a slight increase for the upper portion compared to neat bilayers, are in a
greement with several NMR studies on related systems. The decrease in S-CD
is attributed to a larger accessible volume per lipid in the tail region. S
ignificant changes in the electric properties of the lipid bilayer result f
rom the structural changes, which include a shift and broadening of the cho
line headgroup dipole (P-N) orientation distribution. Our findings reconcil
e apparent controversial conclusions from experiments on diverse lipid syst
ems.