Efficient free energy calculation of water across lipid membranes

Keiko Shinoda, Wataru Shinoda, and Masuhiro Mikami

J. Comput. Chem. 29, 1912-1918 (2008).

An efficient free energy calculation of a water molecule to go across lipid membranes is presented. Both overlapping distribution and cavity insertion Widom methods are complementarily used. The former is useful for a dense region where water molecules are found, i.e., from the interfacial to bulk water region, while the latter works well in the low density region, i.e., the hydrocarbon region. Since both methods evaluate the excess chemical potential of water, the obtained free energy profile is free from the fitting problem usually arisen when a free energy difference method is used. A diphytanyl phosphatidylcholine bilayer is used for our test calculations. An excellent and fast convergence of the chemical potential is obtained when each method is applied for the appropriate region. The estimated free energy barrier using the Ewald method for the electrostatic interaction is 7.2 kcal/mol, which is higher than that using the interaction cutoff of 20Å by about 0.9 kcal/mol.