ABSTRACT
Abstract: The analysis of thermodynamic data concerning solutions using Fluctuation Solution Theory (FST) has provided a deeper understanding of local composition in solution mixtures. Over the past decade, we have used this data to help improve the description of intermolecular interactions implemented in common force elds for molecular simulation, with an emphasis on solutes of biological interest. A comparison between experimental and simulation data for small solute-solvent mixtures provides a clear indication of the quality of the force eld, provides access to solute (and solvent) activities, and thereby helps to ensure that the correct balance between solute-solute, solute-solvent, and solvent-solvent distributions is attained. Here we discuss the advantages and disadvantages of using such an approach for force eld design and parameterization, and provide simulation results for a series of representative solution mixtures obtained with a variety of currently available biomolecular force elds.
