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 (tau) of WALP19, a transmembrane model peptide, in a dimyristoylphosphatidylcholine membrane. The PMF shows a wide range of thermally accessible tilt angles (5 degrees to 22 degrees ) with a minimum at tau=12.5 degrees . The free energy decomposition reveals that the helix tilting up to tau=12.5 degrees is mostly driven by the entropy contribution arising from the helix precession around the membrane normal, whereas the PMF increase after tau=12.5 degrees results from helical deformation due to the sequence-specific helix-lipid interactions.