Exploiting Lipid Permutation Symmetry to Compute Membrane Remodeling Free Energies.
A complete physical description of membrane remodeling processes, such as fusion or fission, requires knowledge of the underlying free energy landscapes, particularly in barrier regions involving collective shape changes, topological transitions, and high curvature, where Canham-Helfrich (CH) continuum descriptions may fail. To calculate these free energies using atomistic simulations, one must address not only the sampling problem due to high free energy barriers, but also an orthogonal sampling problem of combinatorial complexity stemming from the permutation symmetry of identical lipids. Here, we solve the combinatorial problem with a permutation reduction scheme to map a structural ensemble into a compact, nondegenerate subregion of configuration space, thereby permitting straightforward free energy calculations via umbrella sampling. We applied this approach, using a coarse-grained lipid model, to test the CH description of bending and found sharp increases in the bending modulus for curvature radii below 10 nm. These deviations suggest that an anharmonic bending term may be required for CH models to give quantitative energetics of highly curved states.
Department of Theoretical and Computational Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen 37077, Germany.
Greg
G
Bubnis
Department of Theoretical and Computational Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen 37077, Germany.|Chemistry Department, Leibniz Institute of Surface Modification, Leipzig 04318, Germany.|Deptartment of Theoretical Physics, Georg-August University Göttingen, Göttingen 37077, Germany.
Herre Jelger
HJ
Risselada
Department of Theoretical and Computational Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen 37077, Germany.
Helmut
H
Grubmüller
D019277:Entropy; D008051:Lipid Bilayers / Q000737:chemistry*; D008566:Membranes; D056004:Molecular Dynamics Simulation
D008051:Lipid Bilayers