Lipid Bilayer-Membrane Protein Coupling - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 115

lipid interactions resemble the protein lipid vdW and ES interactions found in MD
simulations of a gA channel in phospholipid membranes [ 91 ].
These results suggest that the observed vdW and ES binding energies, which
presumably arise from the electrical properties of both of the participating agents,
do not depend on the molecular net charges. We observe the presence of both vdW
and ES, even in cases where either or both of the participating agents (e.g. PC,
chemotherapy drugs, etc.) have no net molecular charges. Therefore, it is clear that
the interactions appear due to the partial charges on each atom in the drugs or peptides
interacting with lipids on lipid membranes, irrespective of their net molecular charges
[ 24 , 43 , 44 , 53 ]. This hypothesis has appeared in the screened Coulomb interaction
model through the consideration of the localized charges on the participating agents,
irrespective of the consideration of their net molecular charges.

5.8 Discussion and Conclusions

In this chapter, we have investigated the issue of how the hydrophobic coupling
between a lipid bilayer and integral channels regulates the channel stability, using
two structurally different gramicidin A and alamethicin channels as primary exam-
ples. Conformational changes of both trans-bilayer dimerized linear gramicidin A
channels and 'barrel-stave' pore type alamethicin channels are regulated mainly by
the bilayer channel coupling energetics. Experimental results show that an increased
hydrophobic mismatch between bilayer thickness and channel length ( d 0 − l ) appears

as a major channel destabilizing factor. Increased negative lipid curvature and lipid
charge also induce considerable destabilization into channel formation. To theo-
retically address the observed lipid bilayer-induced regulation of channel stability,
we have developed a simple physical model of the 'screened Coulomb interaction',
which has been used to calculate the binding energy of a gramicidin A dimer with a
lipid bilayer required for the stability of the channel structure. The model calculates
the binding energy, considering mainly the electrical properties of both the lipids on
the bilayer and the channel-forming agents. The same model can be extended to also
calculate the binding energy of an alamethicin channel with a lipid bilayer. In this
screened Coulomb interaction model, the calculation of the binding energy of a chan-
nel with a lipid bilayer considers most of the relevant properties such as the localized
charges of both peptides and lipids, geometry of the environment (bilayer thickness,
channel length, channel cross-sectional area, lipid head group cross-sectional area,
lipid intrinsic curvature), the change in the dielectric constant (relative to the aqueous
phase) of the hydrophobic region near the channel interface, and a specific mechan-
ical property such as bilayer elasticity. Changes in any of these properties modulate
the binding energy between the bilayer and the channel, which alters the channel's
stability. We have compared the model results directly with the experimental results
on stability and energetics of the gramicidin A and alamethicin channels in lipid
bilayers, and have found them to be in very good agreement.