| This thesis demonstrates the importance of electronic effects in the solvation of biomolecules. These effects consist of intramolecular charge flow, or polarization, and intermolecular charge transfer. It is shown that both effects significantly impact the energetics and charge distribution of small hydrogen bonded clusters and solvated proteins.;Ab initio calculations on clusters of water with acetate, methylammonium, and dimethylphosphate showed that charge was transferred from the hydrogen bond acceptor to the hydrogen bond donor. The total amount of charge transferred was small, but increased linearly with the number of hydrogen bonds between the solute and water molecules. The transfer of charge was not a computational artifact, since charge was also transferred in the absence of the basis set superposition error. Semiempirical AM1 and PM3 charge distributions of small hydrogen bonded clusters correlated well with the charge distributions obtained from high level MP2 calculations.;A new semiempirical interaction energy decomposition method was developed to decompose interaction energies into electrostatic, polarization and charge transfer components. For AM1 and PM3, polarization contributed ∼10% of the total interaction energy, and charge transfer up to ∼60% of the total interaction energy in small hydrogen bonded clusters.;Charge transfer is also shown to be the main contributor to the protein-water interaction energy for solvated major cold shock protein A (CspA). In solvated CspA ∼2 electrons were transferred from the protein to the first solvation layer via hydrogen bonds. Charge transfer decreased the charge separation of the system: negatively charged residues lost electrons, while positively charged residues gained electrons. Polarization increased the charge separation of the system.;A study of the folding intermediates of betanova showed that polarization and charge transfer depend on the local configuration only. The effect of charge transfer on the charge distribution of betanova was fitted to a simple exponential function of the hydrogen bonding distance between protein and water. The energetic effects of polarization and charge transfer were large, but roughly constant during the protein folding process. Fluctuations in the protein-water interaction were mainly due to the electrostatic energy. Thus, the energetic contribution to the folding of betanova was mainly electrostatic. |
