Structure-spectra correlations in protein infrared spectroscopy are well established. Features observable in the amide I region of the spectrum (similar to1600-1700 cm(-1)) correspond well with alpha-helical (similar to1645 cm(-1)) and beta-sheet (similar to1610 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: alpha-helical and beta-sheet residues that are buried or solvent-accessible. We employed a quantum mechanics/molecular mechanics model using the EDFl 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.