Free energy analysis along the stalk mechanism of membrane fusion.
The free energy profile of the stalk model of membrane fusion has been calculated using coarse-grained molecular dynamics simulations. The proposed method guides the lipid configuration using a guiding wall potential to make the transition from two apposed membranes to a stalk and a fusion pore. The free energy profile is obtained with a thermodynamic integration scheme using the mean force working on the guiding wall as a response of the system. We applied the method to two apposed flat bilayers composed of dioleoyl phosphatidylethanolamine/dioleoyl phosphatidylcholine expanding over the simulation box under the periodic boundary conditions. The two transition states are identified as pre-stalk and pre-pore states. The free energy barrier for the latter is confirmed to be in good agreement with that estimated by the pulling method. The present method provides a practical way to calculate the free energy profile along the stalk mechanism.
Health Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), 1-8-31, Midorigaoka, Ikeda, Osaka 563-8577, Japan. w.shinoda@aist.go.jp.
Shuhei
S
Kawamoto
Wataru
W
Shinoda
D008051:Lipid Bilayers / Q000737:chemistry*; D008561:Membrane Fusion; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; C017251:1,2-oleoylphosphatidylcholine