There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
A statistical thermodynamic approach is used to analyze the various contributions
to the free energy change associated with the insertion of proteins and protein fragments
into lipid bilayers. The partition coefficient that determines the equilibrium distribution
of proteins between the membrane and the solution is expressed as the ratio between
the partition functions of the protein in the two phases. It is shown that when all
of the relevant degrees of freedom (i.e., those that change their character upon insertion
into the membrane) can be treated classically, the partition coefficient is fully
determined by the ratio of the configurational integrals and thus does not involve
any mass-dependent factors, a conclusion that is also valid for related processes
such as protein adsorption on a membrane surface or substrate binding to proteins.
The partition coefficient, and hence the transfer free energy, depend only on the
potential energy of the protein in the membrane. Expressing this potential as a sum
of a "static" term, corresponding to the equilibrium (minimal free energy) configuration
of the protein in the membrane, and a "dynamical" term representing fluctuations around
the equilibrium configuration, we show that the static term contains the "solvation"
and "lipid perturbation" contributions to the transfer free energy. The dynamical
term is responsible for the "immobilization" free energy, reflecting the loss of translational
and rotational entropy of the protein upon incorporation into the membrane. Based
on a recent molecular theory of lipid-protein interactions, the lipid perturbation
and immobilization contributions are then expressed in terms of the elastic deformation
free energy resulting from the perturbation of the lipid environment by the foreign
(protein) inclusion. The model is formulated for cylindrically shaped proteins, and
numerical estimates are given for the insertion of an alpha-helical peptide into a
lipid bilayer. The immobilization free energy is shown to be considerably smaller
than in previous estimates of this quantity, and the origin of the difference is discussed
in detail.