DFT-Based Simulations of Ir Amide I’ Spectra for a Small Protein in Solution

Abstract

Infrared (IR) amide I’ spectra are widely used for investigations of the structural properties of proteins in aqueous solution. For analysis of the experimental data it is necessary to separate the spectral features due to the backbone conformation from those arising from other factors, in particular the interaction with solvent. We investigate the effects of solvation on amide I’ spectra for a small 40-residue helix-turn-helix protein by theoretical simulations based on density functional theory (DFT). The vibrational force fields and intensity parameters for the protein amide backbone are constructed by transfer from smaller hepta-amide fragments; the side-chains are neglected in the DFT calculations. Solvent is modeled at two different levels: first as explicit water hydrogen bonded to the surface amide groups, treated at the same DFT level, and, second, using the electrostatic map approach combined with molecular dynamics (MD) simulation. Motional narrowing of the spectral bandshapes due to averaging over the fast solvent fluctuation is introduced by use of the time-averaging approximation (TAA). The simulations are compared with the experimental amide I’, including two 13-C isotopically edited spectra, corrected for the side-chain signals. Both solvent models are consistent with the asymmetric experimental bandshape, which arises from the differential solvation of the amide backbone. However, the effects of 13-C isotopic labeling are best captured by the gas phase calculations.