Shuhei Kawamoto and Wataru Shinoda
Soft Matter, 10, 3048-3054 (2014).
The free energy profile of the stalk model of membrane fusion has been calculated using coarse-grained molecular dynamic 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 condition. 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.