The role of solvent-induced forces in biomolecular function and stability

Abstract

Solvent-induced forces (SIFs) have been for a long time erroneously related to the presence of more or less uniform “hydration shells”, consisting of more or less permanently bound water molecules. As such misconceptions fade away, it becomes clear that hydration should be viewed statistically and in terms of topological rather than geometric order, and that minor changes (due to solutes) in the structural-rearrangement times of the solvent can reflect major effects in SIFs. Recent work on SIFs at our laboratory, here critically summarized, shows: i) Precisely localized average intramolecular SIFs adjusting the operation of a protein to just what is physiologically required. ii) The involvement of SIFs in the thermodynamic stability of biomelecular solutions and “soups” and related fluctuation behaviour. Sustained, undamped fluctuations occurring in the instability region, and also subcritical ones, occurring close to (yet, not in) the instability region, have been shown to be capable of triggering important concentration- dependent biomolecular processes, iii) The involvement of large numbers of water molecules (of the order of 100) in intra- and interbiomolecular SIFs. This dramatically expands the dimensionality and extension of the functional phase space and helps understand for the first time the extraordinary thermodynamic functional stability of biomolecules.