Lipid Bilayer-Membrane Protein Coupling - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 119

interactions, we have formulated a relatively simple and tractable method, and
avoided the previously encountered complications in a method of calculating the
elastic bilayer deformation energy [ 21 , 38 , 40 , 66 , 67 , 74 ] based on the assump-
tion of complicated individual contributions from the intrinsic monolayer curvature,
local compression and bending moduli of two bilayer leaflets, and the associated
energy densities [ 34 , 63 ]. The molecular dynamics simulations of gramicidin A in
lipid bilayers utilizing an all-atom force field [ 2 ] and computation of the potential
of mean force in a lipid mediated protein-lipid hydrophobic coupling [ 23 ] helped us
confirm that the lipid head group region effectively regulates the lipid bilayer gram-
icidin A channel hydrophobic coupling. The acyl chains may also produce some
direct partial pressure profile on the gramicidin A channels at the channel bilayer
interaction sites, but that should be averaged out by their contributions from all sides
of a gramicidin A channel. One very important insight gained through the model
is that the bilayer imposed dissociation force on gramicidin A channel increases
(and as a result, the gramicidin A channel lifetime decreases) at least exponentially,
which matches with the experimental observations (see Fig. 5.3 and [ 6 , 56 ]). The
experimental observation of increasing the negative lipid curvature-induced linear
decrease in gramicidin A channel stability verified by the theoretical results also
provides evidence in favor of the approach of regulating membrane protein func-
tions due to the hydrophobic energetic membrane-membrane protein coupling. In
the alamethicin channel, the requirement of higher orders of concentration

[ M Alm ]

in thicker lipid bilayers may compensate for the huge variation in G I , II ,butthe

G 1 → 3 of
any alamethicin channel within a lipid bilayer system correspond to a little variation
in the theoretical values of

G 1 → 2 and

experimentally observed small changes in the free energies

G I , II for alamethicin channels consisting of different
numbers of monomers. It should also be stressed that the model calculation is valid
for an arbitrary hydrophobic mismatch between bilayer thickness and channel length
and is equally applicable to at least two types of protein-lined channels, i.e. linear
β -helical gramicidin A type and 'barrel-stave' pore alamethicin type. We have found
very good agreements between the results on channel stability/lifetime emerging
from the binding energy calculation using screened Coulomb interactions and the
experimental observations on gramicidin A and alamethicin channels. The molecular
dynamics simulations also suggest the presence of distance-dependent electrostatic
and van der Waal's interactions between lipids and membrane active agents (peptides
or other biomolecules like chemotherapy drugs, nucleic acid oligomers, or aptamers,
etc.). These simulation results also support the existence of interactions between
the membrane and active agents, due primarily to their electrical properties. The
use of the screened Coulomb interaction model in the membrane-membrane protein
energetics is also supported by molecular dynamics simulations. This theoretical
screened Coulomb interaction model calculation can therefore be generally applied
to the energetics and dynamics of several kinds of membrane proteins with a variety
of membrane effects, as long as they are hydrophobically coupled with lipid bilayers.
Finally, we conclude that the physical lipid-membrane protein interactions, due
mainly to their electrical properties and the related energetics, appear as primary reg-
ulators of membrane protein functions. A membrane's elasticity helps it to bend, due