EVALUATING TWO MODELS FOR THE EFFECTS OF OSMOLYTES ON PROTEIN STABILITY AND FUNCTION: MEASURING THE INTERACTIONS OF GLYCINE BETAINE WITH CARBOXYLIC ACIDS

The osmophobic effect has been the dominant explanation for several decades for why osmolytes stabilize proteins under various stresses. Two competing models have been put forward to attempt to quantify the osmophobic effect. The group transfer free energy model (GTFE) predicts that the primary effects of osmolytes are through interactions with the protein backbone, while interactions with side chains are a minimal, secondary effect. The local-bulk domain partitioning model (LBD) was developed to additionally quantify osmolyte effects on protein-nucleic acid interactions. This model predicts large effects from interactions of osmolytes with negatively charged atomic surfaces. We have been exploring the discrepancies between these models through examining the effects of glycine betaine on the solubility of glutamic acid. We have improved our methodology and begun collecting solubility data as a function of pH. A published comparison of the two models concluded that the LBD model is more accurate than the GTFE model. Our results continue to indicate that errors in the GTFE model may be due, in large part, to a small number of errors in published data, particularly the measurement of glutamic acid and aspartic acid solubility