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

The interpretation of protein amide I infrared spectra has been greatly assisted by the observation that the vibrational frequency of a peptide unit reports on its local electrostatic environment. However, the interpretation of spectra remains largely qualitative due to a lack of direct quantitative connections between computational models and experimental data. Here, we present an empirical parameterization of an electrostatic amide I frequency map derived from the infrared absorption spectra of 28 dipeptides. The observed frequency shifts are analyzed in terms of the local electrostatic potential, field, and field gradient, evaluated at sites near the amide bond in molecular dynamics simulations. We find that the frequency shifts observed in experiment correlate very well with the electric field in the direction of the C=O bond evaluated at the position of the amide oxygen atom. A linear best-fit mapping between observed frequencies and electric field yield sample standard deviations of 2.8 and 3.7 cm(-1) for the CHARMM27 and OPLS-AA force fields, respectively, and maximum deviations (within our data set) of 9 cm(-1). These results are discussed in the broader context of amide I vibrational models and the effort to produce quantitative agreement between simulated and experimental absorption spectra.