Quantifying Interactions between Biochemical Functional Groups and with Hofmeister Salt Ions in Water

Abstract

Interactions between biochemical functional groups are fundamental to biopolymer self-assembly processes and enzyme-substrate binding and ligand binding, and a key determinant of biopolymer structure and function. To date little quantitative information has been available about their strengths and contributions to stability. Interactions of small solutes have been shown to be composed of additive contributions from interactions of one solute with individual function groups on the other solute (one way interactions). Here we test the hypothesis that solute-solute interactions in water can be dissected using additivity and either an ASA or weighted group-based analysis into contributions from group-group interactions (two way analysis). Data for preferential interactions (μ23 values) of amides with other amides and with aromatics and nucleobases as well as for interactions of alcohols and polyols with aromatics and nucleobases are obtained by osmometry and solubility assays and interpreted to obtain two way potentials (alpha values) for the group group interactions. Some of the most favorable interactions are those that correspond to hydrogen bonding between NH and C=O groups like those in protein 2o structures and in DNA/RNA duplexes. The interaction of aromatic C with amide O is very favorable, providing a second example of a favorable n-π∗ interaction, like that of amide C with amide O (Ref 1).Interactions of amides with Na+ and K+ salts of Hofmeister anions reveal that interactions of these salts with hydrocarbon C and amide N, follow the Hofmeister order (KSCN > KCl > KF; NaClO4 > NaCl > Na2SO4). These data quantify interaction of these salts with the most important protein groups and are useful to interpret or predict Hofmeister effects on protein unfolding m-values.1) Bartlett GJ, Choudhary A, Raines RT, Woolfson DN (2010) Nat Chem Biol 6:615–620.