Kristy L. Mardis, Ph.D.
Electron transfer (ET) reactions crucial for a wide range of biologically important processes including photosynthesis and respiration. In photosynthesis and respiration, ET reactions require an organized assembly of proteins. Our long-term goal is to determine the role of protein conformation on ET. This requires the construction and investigation of model supramolecular assemblies capable of ET. Our hypothesis is that c-type cytochromes will provide such a model system. We base this hypothesis on three observations: 1.) they are involved in the respiratory processes of almost all organisms, 2.) some can self-assemble into chains, and 3.) they are capable of electron transfer when bound to certain small molecules.
Multi-domain c-cytochromes have applications as components in bio-mimetic energy storage devices as electric wires or catalytic sites. Detailed structural information about these supramolecular architectures would provide insight into the role of conformation in ET reactions and their suitability as ET agents. To resolve the structure of these complexes in their biological environment (aqueous solutions) wide-angle x-ray scattering techniques are employed. However, this technique requires the construction of molecular models to interpret the experimental data. Hence, the specific goal of the proposed work is to use molecular dynamics to create such models, calculate their x-ray scattering patterns, and by comparison to the experimental data, provide an atomic level picture of c-type cytochrome complexes. In this pilot project, we will: 1) Elucidate the structure of di-, tri-, and tetramers of cytochrome c7 by construction of conformation models via solution phase molecular dynamics calculations and comparison of the calculated and experimental scattering data. 2) Acquire sufficient data to allow submission of a SC1-type proposal.
Successful completion of this work will illuminate the role of conformation in ET and the suitability of cytochrome c7 complexes as building blocks for energy storage devices. Relevance to Public Health: The current study focuses on evaluating a self-assembling system that has been proposed as a new solar energy storage device. More efficient solar energy systems would allow a reduction in fossil fuel usage which, due to its contribution to air pollution, has been linked to increasing respiratory disorders.
K. L. Mardis, “Can configuration Entropy Losses Be Predicted from the Binding Affinities of Hydrogen-Bonded Complexes with Varying Numbers of Single Bonds?” J. Phys. Chem. 110(2), 971 (2006).
K. L. Mardis, R. Luo, M. K. Gilson, “Interpreting Trends in the Binding of Cyclic Urea to HIV-1 Protease.” J. Mol Bio. 309, 507 (2001)
K. L. Mardis, B. J. Brune, P. Vishwanath, B. Giorgis, G. F. Payne, and M. K. Gilson, “Intramolecular versus Intermolecular Hydrogen Bonding in the Adsorption of Aromatic Alcohols onto an Acrylic Ester Sorbent.” J. Phys. Chem. B. 104, 4735 (2000)
J. Glemza, K. L. Mardis, A. A. Chaudhry, M. K. Gilson, and G. F. Payne. “Competition between Intra- and Inter-molecular Hydrogen Bonding.” Ind. Eng. Chem. Res., 39, 463 (2000)
K. L. Mardis, L. David, R. Luo, M. Potter, G. Payne and M. K. Gilson, “Modeling Molecular Recognition: Method and Applications” J. Biomolecular Struct. & Des., Conv. 11, 1 (1999)
K. L. Mardis, A. J. Glemza, B. J. Brune, G. F. Payne, and M. K. Gilson, “The Differential Adsorption of Phenol Derivatives onto a Polymeric Sorbent: A Combined Molecular Modeling and Experimental Study.” J. Phys. Chem. B., 103, 9879 (1999)
K. L. Mardis and E. L. Sibert. “The Effect of Nonadiabatic Coupling on the Calculation of N(E,J) for the Methane Association Reaction.” J. Chem. Phys. 109, 8897 (1998).
K. L. Mardis and E. L. Sibert. “The Effectiveness of Newton’s Method for Improving Ab Initio Force Fields with Applications for CO2 and H2CO.” J. Molec. Spec. 187, 167 (1998).
K. L. Mardis and E. L. Sibert. “Derivation of Rotation-Vibration Hamiltonians that Satisfy the Casimir Condition.” J. Chem. Phys. 106, 6618, (1997).