An accurate representation of solute-water interactions is necessary for molecular dynamics simulations of biomolecules that reside in aqueous environments. We introduce a method for optimizing solute-water van der Waals interactions to reproduce experimental solvation free energy data, and apply it to the optimization of a fixed charge force field (AMBER ff99SB/GAFF) and advanced water model (TIP4P-Ew).  We show that with these optimizations, the combination of AMBER ff99SB/GAFF and TIP4P-Ew is able to reproduce the solvation free energies of a variety of biologically-relevant small molecules to within kBT. We further validate these optimizations by examining the structures of dipeptide-water solutions, the conformational preferences of short disordered peptides, and the native state stability and dynamics of a folded protein. We also introduce a new inexpensive AMOEBA (iAMOEBA) polarizable water model that is more broadly applicable and transferable to various interface chemistries.

New force fields for molecular processes at liquid interfaces

244th National Meeting (2012)

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