Relating the infrared absorption of proteins to their structure - dependence of the transition dipole moment on the protein structure
Title: Relating the infrared absorption of proteins to their structure - dependence of the transition dipole moment on the protein structure
SNIC Project: SNIC 2021/5-567
Project Type: SNIC Medium Compute
Principal Investigator: Andreas Barth <>
Affiliation: Stockholms universitet
Duration: 2022-01-07 – 2023-02-01
Classification: 10603 10402 10302


The leading application of infrared spectroscopy in the life sciences is the analysis of protein structure. It exploits the conformational sensitivity of the amide I vibrations, which are collective vibrations of the amide groups of the protein backbone. However, their theoretical description is incomplete which limits the interpretation of experiments. Therefore, a reliable theoretical description is desirable and can lead to additional structural insight (e.g. Baronio, Baldassarre, & Barth, PCCP 2019). Present calculations of the amide I spectrum consider each amide group as a local amide I oscillator, which has an intrinsic frequency and which couples with other amide groups. The intrinsic frequencies are affected by the local backbone conformation and elec­trostatic effects including hydrogen bonding. Long-range coupling is described by transition dipole coupling (TDC) between the transition dipole moments (TDMs) of close-by amide I oscillators. The TDM is a vector located on each amide group. It is proportional to the dipole derivative (DD), which is related to the change of dipole moment during the vibration. Once the intrinsic frequencies and the coupling constants are known, the spectrum of the de­localized amide I normal modes can be calculated. This ap­proach describes general trends well, but needs to be improved for detailed structural analysis. These improvements rely on DFT calculations of small peptide systems (up to 21 amide groups, Baronio & Barth, J. Phys. Chem. B 2020). We used the last round of our calculations to explore whether the DD properties depend on secondary structure and H bonding. We want now to complete this work by the following studies that are fundamental for the calculation of the amide I spectrum: a) An effect of conformation on the direction of the DD was found in our recent DFT calculations. We need to study this phenomenon further by using a larger variation of dihedral angles and by exploring whether preceding and following amide group have different effects on the DD of the group in between. We will use tetrapeptides as before and isolate the vibrations of the middle amide group by setting the mass of the other atoms to 1000 u. We will then implement our findings into our program for the calculation of the amide I spectrum of proteins. b) An effect of hydrogen bonding on the DD parameters is also indicated by our previous published work and our recent DFT calculations. We will use the same approach as described under a), but using larger structures (10–21 amide groups), which are already geometry optimized. The specific questions of interest are whether there are different effects of H bonding to the oxygen atom or to the hydrogen atom and whether the helix dipole moment has an effect. For the former question we will select amide groups with only one H bond as group of interest and for the latter we will place the amide group of interest in different positions along the helix.