The role of polarization and charge transfer in the solvation of biomolecules

Herein we demonstrate that charge transfer from the protein to the first so lvation layer is a significant contributor to the total solvation interacti on energy between water and major cold shock protein A (CspA). Interestingl y, we find that polarization and electrostatic interactions are predicted t o be less important in protein-water interactions than charge transfer. Cha rge transfer is most prominent for charged residues, but also occurs betwee n water molecules and the hydrophilic side chains and the carbonyl and amid e groups of the main chain. The route of charge transfer is via hydrogen bo nds between protein and solvent. These results an consistent with recent NM R and X-ray observations, which show that hydrogen bonding interactions hav e a significant covalent character as opposed to the traditional purely ele ctrostatic view.