Solvent-induced forces on a molecular scale: non-additivity, modulation and causal relation to hydration

This work concerns solvent-induced interactions and their most familiar subset, hydrophobic interactions. Molecular dynamics simulations allow the eliciting of: (i) the inherently strong non-additivity of solvent-induced forces (SIFs) in water, caused by the failure of Kirkwoodʹs superposition approximation and (ii) the quantitative microscopically space-resolved relation of SIFs to configurational changes of the solvent caused by solutes. These results provide the ground for understanding quantitatively and microscopically many biologically significant findings related to hydration and SIF modulation. Also, they suggest the existence of highly specific solute-solute interactions and of otherwise forbidden pathways for chemical and biological processes in solution, including protein folding and biomolecular recognition.