Understanding water dynamics near topologically complex solutes

Abstract

The properties of solutes in water (e.g. conformational fluctuations of proteins) are known to depend on the properties of the adjoining solvent. Our understanding of this connection is incomplete, partly because the structural and dynamic proper- ties of water near solutes differ from bulk water in a manner that depends on both solute chemistry and topology. Here we report a study focusing on the least un- derstood of these factors: solute topology. We use classical molecular simulations in explicit solvent to investigate water near disaccharides because disaccharides are small enough for detailed study but show the topological and chemical complexity inherent to large biomolecules. We find that the observed slow down of transla- tion and rotation of local water populations precisely agrees with increases in local hydrophobicity. Moreover, as recently observed in proteins, identical functional groups may interact differently with water depending on the chemistry and topol- ogy of neighboring groups. To understand these observations we investigate the mechanism of hydrogen bond exchange for waters within the sugar first solvation shell. Recent reports indicate that rotation of water in bulk occurs through large angular jumps involving bifur- cated hydrogen bond intermediates. The rotational slow down of water near small solutes can be predicted using transition state theory, by accounting for the decrease in the accessible transition state volume and changes the enthalpy of the hydrogen bonds relative to bulk. For our larger solutes we find that accounting for these two factors is insufficient because of unnintuitive changes in the free energy landscape associated with water rotation - reduction in the number of available reactant states and broadening of the transition state. Simple scaling considerations from bulk fail to capture these changes for all but the simplest solute topologies, effectively making water dynamics system dependent.