Development and Validation of Transferable Amide I Vibrational Frequency Maps for Peptides

Abstract

Infrared (IR) spectroscopy of the amide I band has been widely utilized for the analysis of peptides and proteins. Theoretical modeling of IR spectra of proteins requires an accurate and efficient description of the amide I frequencies. In this paper, amide I frequency maps for protein backbone and side chain groups are developed from experimental spectra and vibrational lifetimes of N-methylacetamide and acetamide in different solvents. The frequency maps, along with established nearest-neighbor frequency shift and coupling schemes, are then applied to a variety of peptides in aqueous solution and reproduce experimental spectra well. The frequency maps are designed to be transferable to different environments; therefore, they can be used for heterogeneous systems, such as membrane proteins.

Solvent and conformation dependence of amide I vibrations in peptides and proteins containing proline

“…In predicting spectral line shapes this combined parametrization works in excellent agreement with the experiments, apart from a systematic shift in the peak position [29,32,56,61]. Recently, empirical maps [57] have been developed for the amide I vibrations in the backbone and side chains of proteins. This was done using the experimental spectra and the vibrational life time of NMA and acetamide in both polar and non-polar solvents.…”

Optimization of Model Parameters for Describing the Amide I Spectrum of a Large Set of Proteins

“…74 The approach of utilizing dipeptide ab initio data to calculate the effect on the intrinsic frequency exerted by the nearest neighbor residues has been implemented in several simulations of short polypeptides. 24,29,60,85 Ge and co-workers have, however, shown that this approach leads to worse agreement with experimental results than using only electrostatic methods for simulation of amide I spectra of an octapeptide. 86 In an attempt to evaluate such published maps, we used the DFT map by La Cour Jansen et al 60 for the intrinsic frequency shifts without any modification and re-optimized all other parameters.…”

“…Furthermore, the polypeptide is simplified to a chain of linked peptide units, which means that side chain contributions to the absorption in the amide I range and the coupling between side chain vibrations and the amide I vibrations are neglected. Recent procedures for amide I simulations have simulated also the amino acid absorption 85 or subtracted this contribution from the experimental spectrum used for comparison. 37 Subtraction of the intensity originating from the amino acids is however not a straight-forward procedure as the absorption will be influenced by the protein environment in which they are immersed, 2 and was therefore not In the same way, FSE takes care of small errors in the subtraction of the absorption of the water bending vibration.…”

Electrostatic frequency shifts in amide I vibrational spectra: Direct parameterization against experiment

“…More recently, the advent of two-dimensional infrared (2DIR) spectroscopy has begun to assist in overcoming amide I spectral congestion, [8][9][10] while on the theoretical front, spectroscopic "maps" linking protein structure to specific spectral features have greatly improved our ability to interpret experimental data. [11][12][13][14][15][16][17][18][19] Spectroscopic maps translate protein structural and electrostatic information from classical force field simulations into vibrational frequencies and couplings between peptide groups which allow prediction of infrared spectra. To describe multidimensional IR spectra, Hamm et al 9 extended the normal mode descriptions of Miyazawa 20 and Krimm 21 to a weakly anharmonic exciton model, in which individual amide bonds are assigned isolated carbonyl stretch frequencies (site energies) and pairwise coupling constants to produce …”

“…9 Although simple in form, the accurate structure-based parameterization of this Hamiltonian is non-trivial and has been the subject of numerous computational studies. [11][12][13][14][15][16][17][18][19][22][23][24][25][26] Siteto-site coupling constants are generally extracted by a combination of electrostatic models (e.g., dipole-dipole 22,27 or transition charge coupling 11,13,15,28 ) and DFT-parameterized dihedral maps for nearest-neighbor interactions. 11,13,18,22,26 Site energy maps are based on the observation that electrostatic interactions (particularly hydrogen bonding) between a solvated molecule and its environment are the primary predictors of local vibrational frequencies.…”