BPS2026 – Isomers of common compatible osmolytes are not osmolytic

We assert that nature has conserved the upregulation of compatible solutes that best optimize a preferential solvation model of interaction for combating thermal stress. In particular, we aim to demonstrate why some molecules are commonly employed as compatible solutes, while their stereochemical homologs are not widely produced. We use molecular simulation to screen interactions between target molecules and model proteins systems, and calorimetry and spectroscopy are used to measure interactions and osmolyte structural enhancement of biomolecules. We find that molecules, which interact weakly and non-specifically with proteins, are most successful at promoting the solvent mediated structural enhancement central to the preferential solvation theory.