PHYSICS AND BIOPHYSICS OF SOLVENT-INDUCED FORCES - HYDROPHOBIC INTERACTIONS AND CONTEXT-DEPENDENT HYDRATION

Solvent induced forces (SIFs) among solutes derive from solvent struct ural modification due to solutes, and consequent thermodynamic drive t owards minimization of related free energy costs. The role of SIFs in biomolecular conformation and function is appreciated by observing tha t typical SIF values fall within the 20-200 pN interval, and that prot eins are stable by only a few kcal mol(-1) (1 kcal mol(-1) corresponds to 70 pN Angstrom). Here we study SIFs, in systems of increasing comp lexity, using Molecular Dynamics (MD) simulations which give time-and space-resolved details on the biologically significant scale of single protein residues and sidechains. Of particular biological relevance a mong our results are a strong modulability of hydrophobic SLFs by elec tric charges and the dependence of this modulability upon charge sign. More generally, the present results extend our understanding of the r ecently reported strong context-dependence of SIFs and the related pot ential of mean force (PMF). This context-dependence can be strong enou gh to propagate (by relay action) along a composite solute, and to rev erse SIFs acting on a given element, relative to expectations based on its specific character (hydrophobic/ philic, charged). High specifici ty such as that of SIFs highlighted by the present results is of cours e central to biological function. Biological implications of the prese nt results cover issues such as biomolecular functional interactions a nd folding (including chaperoning and pathological conformational chan ges), coagulation, molecular recognition, effects of phosphorylation a nd more.