Change in a protein's electronic structure induced by an explicit solvent: An ab initio fragment molecular orbital study of ubiquitin

The effect of solvation on the electronic structure of the ubiqutin protein was analyzed using the ab initio fragment molecular orbital (FMO) method. FMO calculations were performed for the protein in vacuo, and the protein was immersed in an explicit solvent shell as thick as 12 Å at the HF or MP2 level by using the 6‐31G* basis set. The protein's physical properties examined were the net charge, the dipole moment, the internal energy, and the solvent interaction energy. Comparison of the computational results revealed the following changes in the protein upon solvation. First, the positively charged amino acid residues on the protein surface drew electrons from the solvent, while the negatively charged ones transfer electrons to the solvent. Second, the dipole moment of the protein was enhanced as a result of the polarization. Third, the internal energy of the protein was destabilized, but the destabilization was more than compensated for by the generation of a favorable protein–solvent interaction. Finally, the energetic changes were elicited both by the electron correlation effect of the first solvent shell and by the electrostatic effect of more distant solvent molecules. These findings were consistent with the picture of the solvated protein being a polarizable molecule dissolved in a dielectric media. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007