Influence of Electrostatic Environment on the Vibrational Frequencies of Proteins

Abstract

Structure-spectra correlations in protein infrared spectroscopy are well established. Features observable in the amide I region of the spectrum (∼1600-1700 cm -1 ) correspond well with R-helical (∼1645 cm -1 ) and β-sheet (∼1610 and 1690 cm -1 ) structure. To provide a better theoretical understanding of how structure and spectra relate, in this work, we have studied how the electrostatic environment of a protein affects the vibrational characteristics of two small amide molecules (trans-N-methylacetamide and N-acetylglycine-N′-methylamide) when they replace residues at structurally diverse locations within the protein. Four representative environments were examined: R-helical and β-sheet residues that are buried or solvent-accessible. We employed a quantum mechanics/molecular mechanics model using the EDF1 density functional with the 6-31+G* basis set as the quantum calculation and CHARMM22 atom-centered charges for the molecular mechanics model. The electrostatic environment generated by the point charges has a significant effect on the vibrational frequencies, lowering their values from gas-phase values into the typical protein range. The local structure of the protein also has a substantial effect. Finally, calculations incorporating a cage of point charge water molecules showed that solvent can have a profound effect near the surface of the protein.

Modeling the amide I bands of small peptides

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] This region is particularly interesting, because the absorption is strong. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] This region is particularly interesting, because the absorption is strong.…”

Charge-state resolved mid-infrared spectroscopy of a gas-phase protein

“…1 However, calculations for small model systems suggest that there is a blue shift of this vibrational band of between 10 and 80 cm À1 upon going from the solution to the gas phase. 21 The amide I band observed here near 1660 cm À1 falls in the range where mainly a-helices are found in solvated proteins. Consistent with this result, about half of the backbone of equine cytochrome c (which has only three point mutations with respect to bovine cytochrome c 22 ) has an a-helix secondary structure 23 and a significant fraction of this secondary structure is retained in a denaturing solution 24 as well as in the gasphase charge states under investigation here.…”

Empirical modeling of the peptide amide I band IR intensity in water solution

“…As a full ab initio approach is still impossible for larger systems, extensions of this empirical method or a combination of explicit and reaction field solvent models may provide a solution to consideration of solvent effects. 9,17,39 …”