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

Abstract

We present a mixed quantum-classical model for studying the amide I vibrational dynamics (predominantly CO stretching) in peptides and proteins containing proline. There are existing models developed for determining frequencies of and couplings between the secondary amide units. However, these are not applicable to proline because this amino acid has a tertiary amide unit. Therefore, a new parametrization is required for infrared-spectroscopic studies of proteins that contain proline, such as collagen, the most abundant protein in humans and animals. Here, we construct the electrostatic and dihedral maps accounting for solvent and conformation effects on frequency and coupling for the proline unit. We examine the quality and the applicability of these maps by carrying out spectral simulations of a number of peptides with proline in D 2 O and compare with experimental observations.

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

“…26 This is primarily a result of the higher reduced mass of the oscillating unit caused by the replacement of the usual NH moiety with the cyclic N-C bond of the Pro side chain. To explore this effect in our dipeptide data, we added three Procontaining dipeptides to our data set: Pro-Leu, Leu-Pro, and Phe-Pro.…”

“…Although useful for qualitative interpretation, comparison with experimental data is generally limited (at best) to peak shapes and must be assisted by the application of arbitrary frequency shifts to simulated spectra. 11,12,26,[39][40][41][42] The development of accurate spectral maps faces several formidable challenges. At the outset, spectral calculations are limited by the practical requirement to make simplifying assumptions that neglect certain physical features.…”

“…An additional frequency shift parameterized by dihedral (φ, ψ) angles can be included to account for nearest-neighbor interactions assumed to extend beyond simple electrostatics. 11,18,26 In parameterizing the expansion coefficients c i in Eq. (2), generally either the field 12,19,24,26 or the potential 13,14,17,18,25 is chosen to have non-zero coefficients, but not both.…”

“…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.…”

“…[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. 29 Early models for amide I frequencies employed simple geometric criteria such as hydrogen bond count and length; 9,[30][31][32][33] although these models have proven intuitively useful and reasonably accurate for simple calculations, 34 they are generally regarded as insufficient for detailed spectral simulations.…”