(308a) Thermodynamically Dominant Hydration Strutures of Amino Acids

The hydration free energy of an amino acid is decomposed into: a chemical term describing the interactions of the amino acid with the water molecules within a defined coordination sphere, a long range contribution accounting for the remaining less specific solvent solute interactions and a packing term accounting for the formation of a solute free cavity the size of the coordination sphere in bulk water. The chemical term can be further recast as a sum over different n-coordinate states with the n^th term depending on the probability of observing n water molecules in a cavity and the free energy of assembling the n water cluster around the solute, in presence of the outer shell solvent. Such a decomposition could thus be used to delineate the spatial region where chemically specific interactions dominate and the number of water molecules which interact specifically with the solute. These specific interactions could be treated explicitly whereas less intensive continuum like solvation models could be used to describe the long range contribution leading to hybrid explicit/implicit models of solvation. These models would better describe solvation around flexible regions in biomolecules such as protein loops, which are expected to interact strongly with the solvent