| Solute-biopolymer interactions are important throughout biology and experimental biochemistry. Small molecule osmolytes help cells to adapt to environmental stress, and polyethylene glycols and Hofmeister salts are used to crystallize and stabilize proteins against denaturation, and to assemble multi-protein complexes. Despite their importance, the weak noncovalent and excluded volume interactions which underlie solute effects are not well characterized. Here we develop a molecular thermodynamic analysis to quantify noncovalent interactions as a sum of 1) excluded volume (for large solutes) and 2) contributions from pairwise interactions of functional groups, relative to corresponding interactions with hydration water. We obtain an extensive databases of preferential interaction data characterizing the interactions of small nonelectrolytes and Hoffmeister salts with sets of small molecules displaying one or more functional groups present on proteins and/or nucleic acids. From these datasets, we extract pairwise "interaction potentials" quantifying the preferential interactions of Hofmeister salts and functional groups on solutes of biochemical interest with the functional groups of proteins and nucleic acids. We then apply the results of this analysis to interpret and quantitatively predict the interactions of these solutes and salts with protein and nucleic acid surfaces and their on protein, nucleic acid helix formation, and other processes. |
