Transmembrane Helix Tilting: Insights from Calculating the Potential of Mean Force

To explore the microscopic forces governing the helix tilting in membranes, we have calculated the potential of mean force (PMF) as a function of tilt angle (τ) of WALP19, a transmembrane model peptide, in a dimyristoylphosphatidylcholine membrane. The PMF shows a wide range of thermally accessible tilt angles (5° to 22°) with a minimum at τ=12.5°. The free energy decomposition reveals that the helix tilting up to τ=12.5° is mostly driven by the entropy contribution arising from the helix precession around the membrane normal, whereas the PMF increase after τ=12.5° results from helical deformation due to the sequence-specific helix-lipid interactions.