Hydrogen-bond energetics drive helix formation in membrane interfaces

Abstract

The free energy cost Δ 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, ∆ G res that drives folding. There is some debate about the correct value of ∆ G res and its dependence on the hydrophobic moment (μ H) of amphiphilic α-helical peptides. We show how to compute ∆ G res correctly. Using published data for two families of peptides with different hydrophobic moments and charges, we find that ∆ G res does not depend upon μ H. The best estimate of ∆ G res is − 0.37 ± 0.02 kcal mol − 1 . This article is part of a Special Issue entitled: Membrane protein structure and function.