Chemical reactions involving molecules may involve the simple loss or gain of an electron or a proton (H+, a hydrogen atom missing its electron), or the breaking of bonds and the formation of new bonds that result in a new molecule. It is also true that molecules are always vibrating; their bonds act like springs that are constantly stretching, compressing or bending. The vibrational motion of molecules is an important factor in their reactivity and the outcome of chemical reactions. For large molecules like proteins, which can contain hundreds of atoms (carbon, nitrogen, oxygen) and bonds, the role of vibrations on reactivity is difficult to determine. And yet, it is important to understand the role of vibrations in protein chemical properties, as proteins are essential components of all living systems. In this project, funded by the Chemical Structure Dynamics and Mechanism (CSDM-A) program of the Chemistry Division, Professor Paul Champion of Northeastern University is using sophisticated laser techniques to study low-frequency (slow) vibrations and how they influence chemical reactions that facilitate the motion of charges (protons and electrons) in biological systems. These vibrational motions can also be associated with the flow of energy and the changes in structure that take place when large protein molecules like enzymes interact with each other or when smaller molecules bind to the protein and cause a signaling or catalytic response. This work is significant because it will generate fundamental new knowledge at the interface of chemistry and physics that will benefit a variety of biological applications. Within the broad class proteins called heme proteins (where the most well-known examples are hemoglobin and myoglobin)which contain iron atoms. An especially important protein, cytochrome c, which shuttles electrons in the cellular mitochondria (these are the structures of living cells that process energy). A new and very important reaction involving this protein has been recently discovered. Basically, a structural change at the heme iron atom takes place when cytochrome c interacts with the mitochondrial membrane and this reaction initiates apoptosis, a fundamental cellular process that leads to cell death. This is an important topic, which is providing a better understanding of tissue differentiation and development, as well as the evolution of cancer. This project has significance to society at large, because a better understanding of fundamental biochemical processes underpins the ability to make transformational improvements in human health. Students working on this project (both graduate and undergraduate) are being trained in cutting edge optical and biological techniques that benefit society through the enhancement of the human resource infrastructure that is crucial to the academic, medical, biotech, and optical communications industries.

The reaction dynamics of several specific biomolecular and chemical systems involved in charge, group, and energy transport processes is being investigate. One investigation is focusing on proton transport in green fluorescent protein and is testing hypotheses related to both the excited and the ground state reactions. Proton "inventory" experiments will evaluate the participation of multiple protons in ground state tunneling. In the excited state, the temperature and excitation energy dependence of vibrational coherence, energy relaxation, dephasing, and population transfer is being examined. In another investigation, the photophysics that underlies a recent ultrafast x-ray study of ferrous cytochrome c is being investigated. Temperature dependent measurements of methionine (Met80) and NO ligand photolysis in cytochrome c is being carried out and the enthalpic barriers for the rebinding reactions are being determined. The strong vibrational coherence responses predicted for these photoreactions are also being compared. Low temperature kinetic methods are being used to probe the excited state photo-processes of photolyases, enzymes that use blue light to repair several types of ultraviolet-induced DNA damage. Finally, development of a new experimental methodology is focusing on the use of nanopores to probe dynamic allostery, conformational interconversions, and fluctuations of individual proteins. For example, the nanopore methodology is being used to investigate allosteric activation in proteins that regulate DNA transcription as well as protein complexes with effector functions that help to regulate enzyme activity. Proton and electron transport underlie highly evolved biological mechanisms of energy storage and enzymatic catalysis (including DNA photo repair).

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

National Science Foundation (NSF)
Division of Chemistry (CHE)
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Colby A. Foss
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Northeastern University
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