Interactions of Amide Solutes with Biopolymer Functional Groups and Hofmeister Salts

Abstract

Urea and other amides exert large destabilizing effects on noncovalent biopolymer self-assembly and binding. Salt anions and cations from the Hofmeister series exert characteristic stabilizing or destabilizing effects on these processes. Effects of these small solutes and salt ions arise from their favorable or unfavorable interactions with functional groups on the protein or nucleic acid surface exposed. To quantify these interactions, we determine the thermodynamics of interactions of amide solutes with model compounds displaying the functional groups of interest (other amides, aromatic hydrocarbons, nucleobases) and with Hofmeister salts using osmometry or solubility assays. Multivariable linear regression of these and literature data reveals that these solute-functional group interactions are additive and generally independent of context, and yields interaction potentials (α-values) quantifying interactions of each solute with amide, hydrocarbon and nucleobase groups. These results allow us to predict and/or interpret effects of these solutes on protein and nucleic acid processes, and to use these solutes as probes of large conformation changes in transition states and intermediates. Analysis of thermodynamic data for interactions of a series of alkylated ureas with different surface types reveals that favorable interactions with sp2 and sp3 C and N and unfavorable interactions with sp2 O increase with increasing hydrocarbon surface area of the alkylated urea. Interactions of these alkylated amides with a series of Na+ and K+ salts of Hofmeister anions reveal that interactions of the salts with hydrocarbon C and amide N, but not amide O, follow the Hofmeister order (KSCN > KCl > KF; NaClO4 > NaCl > Na2SO4). Additional analysis of these data should provide information regarding free energies of interaction of C, N and O groups in folding, binding and other noncovalent self-assembly processes of proteins.Research is supported by NIH GM47022