Insight into vibrational circular dichroism of proteins by density functional modeling

Abstract

Vibrational circular dichroism (VCD) spectroscopy is an excellent method to determine the secondary structure of proteins in solution. Comparison of experimental spectra with quantum-chemical simulations represents a convenient and objective way to extract information on the structure. This has been difficult for such large molecules where approximate theoretical models have to be used. In the present study we applied the Cartesian-coordinate based tensor transfer (CCT) making it possible to extend the density functional theory (DFT) and model spectral intensities of large globular proteins nearly at quantum-chemical precision. Indeed, comparison with experiment provided a better understanding of the dependence of VCD spectral shapes on the geometry, their sensitivity to fine structural details and interactions with the environment. On a model set of globular proteins the simulated spectra correlated well with experimental data and revealed which structural information can (and cannot) be obtained from this kind of spectroscopy. Although the VCD technique has been regarded as being rather insensitive to side-chain variations, we found that the spectra of human and hen lysozyme differing by a few amino acids only are quite distinct. This has been explained by long-distance coupling of the amide vibrations. Likewise, the modeling reproduced some spectral changes caused by protein deuteration even when the protein structure was conserved.

Recent Trends in Chiroptical Spectroscopy: Theory and Applications of Vibrational Circular Dichroism and Raman Optical Activity

“…As a better alternative, we proposed the Cartesian coordinate‐based tensor transfer (“CCT”), where the vibrational parameters ‐ force field, magnetic and electric dipole derivatives (tensors A and P ) – are calculated for smaller fragments and transferred back on the molecule of interest . This allowed for relatively precise VCD simulations on sizable polypeptides and proteins or nucleic acids . Lately, technologically more advanced molecules‐in‐molecules (MIM) method has been developed and applied on several examples, although systems studied by it were still smaller than allowed by CCT …”

The effect of protein backbone hydration on the amide vibrations in Raman and Raman optical activity spectra

“…Recent studies show that it is very challenging to understand the structure-spectrum relation in much detail. 6,32 It will therefore be very interesting to see further development and more applications of specific methods for solvation 43,45,46,74 and further examine how the side-chains, 32,62 conformational disorder 34 and hydrogen bonding with the solvent all collectively contribute to the calculated spectra of proteins.…”

Instrumentation for Vibrational Circular Dichroism Spectroscopy: Method Comparison and Newer Developments

“…Spectra for structures as large as globular proteins have been successfully simulated using this method [ 153 ]. Alternatively, isotope labeling can be introduced to the peptide sequence to spectrally shift the contributions of a local part of the biopolymer, and with computational modeling of VCD spectra for possible structural variants, local conformations can be deduced [ 100 , 154 , 155 , 156 , 157 , 158 , 159 , 160 ].…”