The objective of this project, jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences and the Experimental Physical Chemistry Program in the Chemistry Division, is to understand the structural nature of the low-frequency normal modes of vibration that control the rate of electron-transfer reactions in proteins. Low-frequency vibrational modes in proteins are of significance to the dynamics of a variety of biological processes, including those of the first events of vision and photosynthesis, because these modes account for the rate-limiting structural rearrangement of the reactant molecules that defines the reaction coordinate. Despite their importance, very little is concretely known about which structures are moving nor is the character of the motion involved in the normal mode of vibration understood. Recent work in the PI's laboratory suggests that intermolecular modes between electronic chromophores and the surrounding protein or solvent are good candidates for the modes that control electron-transfer reactions in proteins. Interactions like these allow a protein to tune the electronic properties and reactivity of the imbedded chromophores. These modes can be detected using a femtosecond time-domain form of resonance Raman spectroscopy called dynamic absorption spectroscopy. This project takes advantage of recent progress made in this laboratory in the detection and analysis of signals arising from low-frequency coherent wave-packet motion on the ground and excited-state potential-energy surfaces of electronic chromophores in solution and in protein hosts. An important finding from this work is that clustered solvent molecules in the first solvation shell of chromophores with delocalized pi-electron systems can be vibronically coupled to the chromophore's pi-to-pi* electronic transition; they obtain resonance Raman activity by attacking the pi-electron density of the chromophore. The initial focus of the research will be on characterization of vibrational coherence of Zn(II)-substituted porphyrins in solution and in two simple protein hosts, cytochrome c and myoglobin. The focus in these studies will be on the ordered polar and non-polar intermolecular interactions of neighboring solvent or amino acid side chains with the pi-electron density of the porphyrin.
The methods and ideas that will be developed in this project are potentially of broad use in the study of chemical dynamics in biological systems, materials, and in condensed phases. The use of strong electronic chromophores in time-resolved spectroscopic studies of protein and solvent dynamics is also of potential importance to the area of protein stability and folding/misfolding. This research will play an integral role in the PI's graduate and undergraduate teaching by providing key lecture topics and applications even in introductory courses. Additionally, the work will provide excellent training for research students at all levels. The work will expose the students to a wide range of disciplines, ranging from structural biology to chemical physics.
