Center for Biomolecular Structure Lecture Series

The long-range structural vibrations of biomacromolecules (molecular weight > 5kDa), are matched to biological thermal energies. This intriguing overlap raises the question if, like sequence and structure, these dynamics are also evolutionarily optimized for robust and efficient biochemistry. The vibrations for such massive systems are necessarily complex. The structural vibrations involve displacements of entire subdomains, are numerous and closely spaced in energy, leading to dense spectra. The spectra are further complicated by the energy overlap with collective excitations of the biological water necessary for in vivo structure and biological relevance. Compounded with these effects, while a single spectrum corresponds to a single structure, biomacromolecular structure thermally samples small configurational changes in time, leading to variation in the vibrational spectra. These effects all lead to the smooth featureless spectra seen by investigators for macroscopic samples. In this talk I will provide an overview of terahertz biomolecular studies and discuss the fundamental issue of isolating vibrational excitations based on specific structural displacements. An example of a technique to provides this isolation is anisotropic terahertz microspectroscopy (ATM). Using ATM we have found that indeed there are biases in the directionality of vibrational displacements which change with ligand binding and photoexcitation. In particular photoexcitation measurements of orange carotenoid protein (OCP) demonstrate that intermediate states of the photo cycle coincide with changes in the directionality of vibrations, suggesting these reorganizations of the dynamics may assist with access to intermediate state structures. Finally, I will discuss the challenges of current instrumentation, computational tools and sample preparation that need to be addressed to more fully realize the potential of THz in the understanding of the role of picosecond structural dynamics in biology.