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

Abstract

The effect of solvation on the electronic structure of the ubiquitin 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 A 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.

Explicit solvation of a single-stranded DNA, a binding protein, and their complex: a suitable protocol for fragment molecular orbital calculation

“…This pattern was invariant regardless of the kind of solute or the calculation method used (MPA or NPA). Similar, if not identical, patterns were seen in the previous FMO studies of a solvated protein (ubiquitin) [9] and dsDNA [17], as well as in a semi-empirical quantum mechanical study of a solvated dsDNA [29]. Note also that the solute net charges were unchanged by neutralization.…”

“…The effects of solvent size on the solutes were systematically investigated by the following scheme: molecular-mechanics (MM)-based modeling and annealing of the solvated molecular structures of the solutes, preparation of the structures for FMO from the MM-modeled structures, and calculation of their electronic structures by FMO. This scheme was basically similar to that of our previous studies on a solvated protein [9] and dsDNA [17], except that in the present study we also examine the effect of neutralization. Note that the distance between a solvent or ion and the solute was measured as the distance between nonhydrogen atoms (Na, Cl, O, C, N, and P) to maintain consistency with the preceding studies.…”

“…The output of the FMO calculations was post-processed similarly to our previous reports [9,17]. The net charges of the solutes were calculated as summations of the net charges of the constituent atoms obtained by either Mulliken population analysis (MPA) or natural population analysis (NPA) [35].…”

“…The minus charge transfer is natural for ssDNA because its formal charge is -5e, but not so for SSB whose formal charge is +2e (Table 1). Minus charge transfer from solutes to solvents were also seen in several FMO and semi-empirical quantum mechanical (QM) calculations of biological molecules [9,17,28,29], in all of which MM-based methods were used for preparation of the molecular structures. Interestingly, plus charge transfer was observed in a QM calculation of bovine pancreatic trypsin inhibitor whose solvated structure was prepared by a QM/MM-MD simulation [38].…”

“…However, it is more realistic to use an explicit solvent model. Hence, FMO calculations have been performed with explicit models for an oligopeptide [8], proteins [9][10][11], ligands [12], protein/ligand complexes [13][14][15], double-stranded (ds) DNAs [16,17], and a protein/dsDNA complex [18]. To the list we would like to add a single-stranded DNA (ssDNA) and its complex with a protein.…”