Density Functional Theory Vibrational Frequencies of Amides and Amide Dimers

Abstract

Infrared spectra of amides and polypeptides can provide detailed information on conformation. An understanding of the amide group in model compounds is a vital step toward a deeper insight into the vibrational spectra of proteins. We show that in contrast to MP2 and the popular B3LYP functional, which overestimate amide I frequencies by 20−80 cm-1, the recently developed empirical density functional, EDF1, yields unscaled harmonic vibrational frequencies of monoamides in close agreement with experimental data, even using the relatively small 6-31+G* basis set. New calculations on several hydrogen-bonded amide dimers and the experimental data available for these dimers also support the conclusion that EDF1 yields frequencies in better agreement with experiment than MP2 or B3LYP. We present calculated minimum-energy structures and vibrational spectra of N-acetylglycine-N‘-methylamide and N-acetyl-l-alanine-N‘-methylamide at the EDF1/6-31+G* and B3LYP/6-31+G* levels.

Close agreement between the orientation dependence of hydrogen bonds observed in protein structures and quantum mechanical calculations

“…Although NMA dimers are routinely used to model main-chain hydrogen bonds, the methyl groups on both ends can contribute significantly to the dimerization energy surface (13,21), and hence formamide is a better model for amino acid side-chain hydrogen bonds. A number of low-energy dimer arrangements (parallel, antiparallel, and out-of-plane) have been described in the literature (17,18,21,22). For comparison with protein side-chain statistics, we used an outof-plane formamide dimer with a single hydrogen bond (Fig.…”

“…1A). Cyclic conformations with two NOH⅐⅐⅐OAC hydrogen bonds occupy global minima for both formamide and NMA dimers (21,22); however, we wanted to model single hydrogen bonds often occurring in proteins, deferring the issue of multiple hydrogen bonds and cooperativity to a later study. The starting geometry for the formamide dimer optimization was taken from ab initio calculations carried out in ref.…”

“…It is a nontrivial problem to choose a small hydrogen bonded dimer that accurately represents hydrogen bonds found in protein side chains and main chains. Formamide, acetamide, N-methylacetamide (NMA), formamide-formaldehyde, and water dimers (and combinations thereof) have been explored in the literature, primarily with the purpose of identifying various local and global minima in a given complex (9,10,(17)(18)(19)(20)(21)(22)(23). Although NMA dimers are routinely used to model main-chain hydrogen bonds, the methyl groups on both ends can contribute significantly to the dimerization energy surface (13,21), and hence formamide is a better model for amino acid side-chain hydrogen bonds.…”

Preferred Configurations of Peptide–Peptide Interactions

“…Due to the delicacy involved in comparisons of different sorts of geometries, with differing origins of stability, it would be injudicious to base any decisions of relative stability on any but high-level correlated calculations, of which there have been several performed in recent years. Concerning studies of peptide analogues such as formamide and N-methylacetamide, the majority were limited primarily to standard H-bonded geometries [25][26][27][28][29] , especially those wherein the two molecules occupied the same plane [30][31][32][33][34] . There have been a handful of works that went beyond this simple paradigm and noted dimer geometries that had significant elements of nonplanarity [35][36][37][38][39] , but did not pursue this issue in any detail.…”

Vibrational spectroscopy and DFT calculations of di‐amino acid peptides: α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu in the solid state

“…The accuracy of structural determination using vibrational spectroscopy depends critically on the selection of vibrational parameters that are sensitive to the changes in conformation. The conformation-sensitive bands in the spectra of polypeptides in water are amide I vibrations, [10,11] amide II vibrations, [12,13] NH stretching vibrations (amide A), [14,15] C α D vibrations, [16] and skeletal vibrations observed in Raman spectra. [17,18] However, the most frequently used bands for structural determination are the amide I and amide III bands.…”