Proteins and nucleic acids may be the movers and shakers of biochemistry, but researchers ignore the subtleties of "uninvolved" solutes at their own peril. There is much anecdotal, but little systematic understanding of how the choice of a particular buffer, salt, or other small solute will effect a biochemical process. Fortunately, systematic understanding is not needed to solve many problems, but as our knowledge of the genome, proteome, and interactome progress, our computer models will require more accurate thermodynamic inputs to fully utilize the predictive power of our exponentially increasing knowledge.
Weak interactions between small solutes are challenging to measure with precision, but techniques such as solubility measurements, osmometry, and isopiestic distillation make the measurements possible. Further, many of these measurements can be performed accurately by new undergraduate researchers in a period of just a few months. We hope to develop protocols to fill in gaps in the systematic understanding of small solute interactions in multicomponent solutions. Such studies will lead to increased precision in the use of small solutes as probes of biomolecule structure, and to improvements in implicit solvent forcefields used pervasively in computational biochemistry.