Electric Interactions and Structural Dynamics of Hydrated Biomolecules Mapped by Ultrafast Vibrational Probes

ended

Biomolecules exist in an aqueous environment of dipolar water molecules and solvated ions. Their structure and biological function are strongly influenced by electric interactions with the fluctuating water shell and ion atmosphere. Understanding such interactions at the molecular level is a major scientific challenge; presently, their strengths, spatial range and interplay with other non-covalent interactions are barely known. Going far beyond existing methods, this project introduces the new paradigm of a direct time-resolved mapping of molecular electric forces on sub-nanometer length scales and at the genuine terahertz (THz) fluctuation frequencies. Vibrational excitations of biomolecules at the interface to the water shell act as sensitive noninvasive probes of charge dynamics and local electric fields. The new method of time resolved vibrational Stark shift spectroscopy with THz external fields calibrates vibrational frequencies as a function of absolute field strength and separates instantaneous from retarded environment fields. Based on this knowledge, multidimensional vibrational spectroscopy gives quantitative insight in the biomolecular response to electric fields, discerning contributions from water and ions in a site-specific way. The experiments and theoretical analysis focus on single- and double-stranded RNA and DNA structures at different hydration levels and with ion atmospheres of controlled composition, structurally characterized by x-ray scattering. As a ground-breaking open problem, the role of magnesium and other ions in RNA structure definition and folding will be addressed by following RNA folding processes with vibrational probes up to milliseconds. The impact of site-bound versus outer ions will be dynamically separated to unravel mechanisms stabilizing secondary and tertiary RNA structures. Beyond RNA research, the present approach holds strong potential for fundamental insight in transmembrane ion channels and channel rhodopsins.