Electron tunneling reactions are critical in photosynthesis, oxidative phosphorylation, drug metabolism, biosynthesis, and catalysis. The success or failure or metabolic pathways depends upon the rates of these reactions, which in turn, are controlled by the structure of the medium between electron donor and acceptor. The means by which proteins, nucleic acids, and protein-protein complexes control these reaction rates will be the subject of our investigations (competitive renewal of Grant R01- GM48043). The influence of protein primary, secondary, tertiary, and quaternary structure, protein/protein docking interactions, and protein dynamics on electron transport rates will be probed using new quantitatively reliable methods in the photosynthetic reaction center/cytochrome c/2 complex, cytochrome c peroxidase/cytochrome c complex, cytochrome b/562 and cytochrome c. In addition, new reduced but exact methods of representing the results of protein electron transfer calculations will produce interpretative tools as simple and intuitive as Pathways analysis, but quantitatively reliable. The ubiquitous nature of electron transfer processes in biosynthesis and energy transduction makes them a natural target for investigation. These investigations involve quantum mechanical tunneling of an electron, and tunneling processes display an exquisite sensitivity to the structure of the barrier being traversed. Therefore, if quantitatively understood, these electron tunneling reactions could be used as diagnostics of macromolecule structure (secondary structure in proteins, DNA lesions, etc.) and could be manipulated in a medical setting to control drug metabolism (by cytochrome P/450) or DNA biosynthesis (by ribonucleotide reductase). This research project will be carried out collaboratively between the University of Pittsburgh Department of Chemistry and the University of California, San Diego Department of Physics. This proposal is intended to allow the continuation of collaborative studies that led to the Pathway model of protein electron transfer reactions, related multi- pathway methods, and their numerical implementations.
| Teo, Ruijie D; Terai, Kiriko; Migliore, Agostino et al. (2018) Electron transfer characteristics of 2'-deoxy-2'-fluoro-arabinonucleic acid, a nucleic acid with enhanced chemical stability. Phys Chem Chem Phys 20:26063-26067 |
| Teo, Ruijie D; Smithwick, Elizabeth R; Migliore, Agostino et al. (2018) A single AT-GC exchange can modulate charge transfer-induced p53-DNA dissociation. Chem Commun (Camb) 55:206-209 |
| Polizzi, Nicholas F; Wu, Yibing; Lemmin, Thomas et al. (2017) De novo design of a hyperstable non-natural protein-ligand complex with sub-Å accuracy. Nat Chem 9:1157-1164 |
| Polizzi, Nicholas F; Therien, Michael J; Beratan, David N (2016) Mean First-Passage Times in Biology. Isr J Chem 56:816-824 |
| Zheng, Lianjun; Polizzi, Nicholas F; Dave, Adarsh R et al. (2016) Where Is the Electronic Oscillator Strength? Mapping Oscillator Strength across Molecular Absorption Spectra. J Phys Chem A 120:1933-43 |
| Polizzi, Nicholas F; Migliore, Agostino; Therien, Michael J et al. (2015) Defusing redox bombs? Proc Natl Acad Sci U S A 112:10821-2 |
| Beratan, David N; Liu, Chaoren; Migliore, Agostino et al. (2015) Charge transfer in dynamical biosystems, or the treachery of (static) images. Acc Chem Res 48:474-81 |
| Jiang, Nan; Kuznetsov, Aleksey; Nocek, Judith M et al. (2013) Distance-independent charge recombination kinetics in cytochrome c-cytochrome c peroxidase complexes: compensating changes in the electronic coupling and reorganization energies. J Phys Chem B 117:9129-41 |
| Balabin, Ilya A; Hu, Xiangqian; Beratan, David N (2012) Exploring biological electron transfer pathway dynamics with the Pathways plugin for VMD. J Comput Chem 33:906-10 |
| Barbee, Jenna; Kuznetsov, Aleksey E (2012) Revealing substituent effects on the electronic structure and planarity of Ni-porphyrins. Comput Theor Chem 981:73-85 |
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