Hydrogen-bond energetics drive helix formation in membrane interfaces

The free energy cost Delta G of partitioning many unfolded peptides into membrane interfaces is unfavorable due to the cost of partitioning backbone peptide bonds. The partitioning cost is dramatically reduced if the peptide bonds participate in hydrogen bonds. The reduced cost underlies secondary structure formation by amphiphilic peptides partitioned into membrane interfaces through a process referred to as partitioning-folding coupling. This coupling is characterized by the free energy reduction per residue, Delta G(res) that drives folding. There is some debate about the correct value Of Delta G(res) and its dependence on the hydrophobic moment (mu(H)) of amphiphilic alpha-helical peptides. We show how to compute Delta G(res) correctly. Using published data for two families of peptides with different hydrophobic moments and charges, we find that Delta G(res) does not depend upon mu(H). The best estimate of Delta G(res) is -0.37 +/- 0.02 kcal mol(-1). This article is part of a Special Issue entitled: Membrane protein structure and function. (C) 2011 Elsevier B.V. All rights reserved.