Understanding the signatures of secondary-structure elements in proteins with Raman optical activity spectroscopy

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.