All Atom Molecular Dynamics Simulations of pH Dependent Surfactants

Molecular dynamics simulations have been widely applied to study surfactant systems. However, traditional methods do not capture the effect of changing pH, as all molecules have a fixed protonation state. Continuous constant pH molecular dynamics (CpHMD), however, allows for atomistic study of pH-coupled phenomena, and has been successfully applied to study proteins. In this work we use CpHMD with pH-based replica exchange to study pH-sensitive surfactants in aqueous solution. Lauric acid, a twelve-carbon fatty acid, self-assembles in a pH-dependent manner, with a bilayer to micelle transition seen near the aggregate's pKa. The calculated pKa of a 0.5 M lauric acid solution is 7.0, in good agreement with the experimental value of 7.5. Decreasing the tail length by four carbons decreases the pKa by ∼0.5 units, in qualitative agreement with experiment. The effect of aggregate size and concentration was also examined. We have also simulated the titration of fatty acids in fully-solvated detergent bilayers, which sets the stage for exploring proton-coupled biological processes in cellular environments.