Free energy of micellization of dodecyl phosphocholine (DPC) from molecular simulation: Hybrid PEACH-BAR method.

A new method to extract the free energy of aggregation versus aggregate size from molecular simulation data is proposed and applied to a united atom model of the zwitterionic surfactant dodecyl phosphocholine in water. This system's slow dissociation rate and low critical micelle concentration (CMC of approximately 1-2 mM) make extraction of cluster free energies directly from simulation results using the "partition-enabled analysis of cluster histogram" (PEACH) method impractical. The new approach applies PEACH to a model with weakened attractions between aggregants, which allows sampling of a continuous range of cluster sizes, then recovers the free energy of aggregation under the original fully-attractive force field using the BAR free energy difference method. PEACH-BAR results are compared with free energy differences calculated via umbrella sampling, and are used to make predictions of CMC, average cluster size, and SAXS scattering profiles that are in fair agreement with experiment.