Electronic Circular Dichroism Spectroscopy of Proteins

Electronic circular dichroism (CD) spectroscopy is an important tool for the elucidation of biomolecular structure. This review describes the latest progress and developments in experimental and theoretical studies of proteins using CD spectroscopy, including time-resolved measurements, oriented CD, and state-of-the-art experiments using polarized UV light from high-energy synchrotron radiation. Statistical and machine learning methods for the analysis of experimental spectra are surveyed. Computational methods employed to predict CD spectra from structure include ab initio quantum chemistry techniques, time-dependent density functional theory, and exciton theory. We describe recent computations using exciton theory, where we outline the importance of electronic-vibrational coupling and the influence of electrostatics of the protein environment on the electronic transitions in the chromophores responsible for CD signals in the near UV. Improvements in the accuracy of the computational approaches should allow more quantitative studies, applying a combination of experimental data and modeling to a variety of interesting questions.