Towards integrative structural biology of proteins at ultra-high resolution

Integrative structural biology is an emerging approach in which results obtained through different experimental methods are integrated using a common computational framework. Thus far, integrative structural biology has focused mainly on resolving large macromolecular complexes and their dynamics. Here we propose to use integrative structural biology to obtain insights at very high structural resolution. We use information from X-ray crystallography and combine it with results from different vibrational spectroscopic approaches, particularly FTIR spectroscopy, Raman spectroscopy, and Raman Optical Activity (ROA) spectroscopy, to better understand photoreceptor proteins. In ROA spectroscopy the detection of differences in Raman scattering when using left polarized light and right polarized light is increasingly allowing insights into functionally important structural distortions of the light-absorbing chromophore at the active site of photoreceptors. These results are then integrated using quantum chemical calculations. We illustrate this approach for two different types of photoreceptors: photoactive yellow protein and microbial rhodopsins.