Understanding the Signatures of Secondary‐Structure Elements in Proteins with Raman Optical Activity Spectroscopy

Abstract

A prerequisite for the understanding of functional molecules like proteins is the elucidation of their structure under reaction conditions. Chiral vibrational spectroscopy is one option for this purpose, but provides only indirect access to this structural information. By first-principles calculations, we investigate how Raman optical activity (ROA) signals in proteins are generated and how signatures of specific secondary-structure elements arise. As a first target we focus on helical motifs and consider polypeptides consisting of twenty alanine residues to represent alpha-helical and 3(10)-helical secondary-structure elements. Although ROA calculations on such large molecules have not been carried out before, our main goal is the stepwise reconstruction of the ROA signals. By analyzing the calculated ROA spectra in terms of rigorously defined localized vibrations, we investigate in detail how total band intensities and band shapes emerge. We find that the total band intensities can be understood in terms of the reconstructed localized vibrations on individual amino acid residues. Two different basic mechanisms determining the total band intensities can be established, and it is explained how structural changes affect the total band intensities. The band shapes can be rationalized in terms of the coupling between the localized vibrations on different residues, and we show how different band shapes arise as a consequence of different coupling patterns. As a result, it is demonstrated for the chiral variant of Raman spectroscopy how collective vibrations in proteins can be understood in terms of well-defined localized vibrations. Based on our calculations, we extract characteristic ROA signatures of alpha helices and of 3(10)-helices, which our analysis directly relates to differences in secondary structure.

MOVIPAC: Vibrational spectroscopy with a robust meta‐program for massively parallel standard and inverse calculations

“…Three positive bands are obtained in case of the p-helix in the wavenumber region from about 1200 to 1300 cm À1 , contrary to the spectra of the a-and 3 10 -helices [77] where alternating negative and positive bands can be observed. The amide I bands between 1600 and 1700 cm À1 in the ROA spectrum of the p-helix are similar to the ones obtained for the a-helix, [77] namely a couplet that is negative at lower wavenumbers and positive at higher wavenumbers. This is exactly opposite to the case of the 3 10 -helix, where in the amide I region a couplet is observed positive at lower wavenumbers and negative at higher wavenumbers, such that this couplet may serve as a signature for 3 10 helices.…”

“…The most obvious difference in the calculated ROA spectrum from 1100 to 1800 cm À1 compared to the spectra of the aand 3 10 -helices (Ref. [77]) are observed in the extended amide III region (i.e., the spectral region between about 1200 to 1300 cm À1 ), which mainly comprises in phase-combinations of NAH bending and CAN stretching vibrations of the amide group and C a AH bending vibrations. Three positive bands are obtained in case of the p-helix in the wavenumber region from about 1200 to 1300 cm À1 , contrary to the spectra of the a-and 3 10 -helices [77] where alternating negative and positive bands can be observed.…”

“…[74,75] For example, this allows one to directly relate the sign of the amide I couplet in ROA spectra to the secondary structure. [77] Furthermore, the coupling constants often show a simple dependence on the molecular structure that can be parameterized to obtain simpler localmode models for predicting vibrational spectra of polypeptides and polymers. [78] The localization of normal modes is implemented in the LocVIB add-on package to SNF, which is included in the MOVIPAC release.…”

“…[77]) are observed in the extended amide III region (i.e., the spectral region between about 1200 to 1300 cm À1 ), which mainly comprises in phase-combinations of NAH bending and CAN stretching vibrations of the amide group and C a AH bending vibrations. Three positive bands are obtained in case of the p-helix in the wavenumber region from about 1200 to 1300 cm À1 , contrary to the spectra of the a-and 3 10 -helices [77] where alternating negative and positive bands can be observed. The amide I bands between 1600 and 1700 cm À1 in the ROA spectrum of the p-helix are similar to the ones obtained for the a-helix, [77] namely a couplet that is negative at lower wavenumbers and positive at higher wavenumbers.…”

Raman spectra from ab initio molecular dynamics and its application to liquid S-methyloxirane

“…KS-DFT was used as the electronic structure method in the framework of the Gaussian and plane waves formalism. We tested three different density functionals: BP86, 48,49 that has been found to perform well in static frequency calculations within the doubleharmonic approximation, [50][51][52][53][54][55][56][57][58][59][60][61][62][63] 73,74 for comparing purposes. BLYP-Goedecker-Teter-Hutter (GTH) (in case of PBE the PBE-GTH) pseudopotentials [75][76][77] and the TZVP-GTH and DZVP-GTH basis sets were applied.…”