This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports the development of novel theory, computational methods and experimental verification to enable the design of proteins capable of electron transfer. Electron transfer reactions are central to bioenergetic processes, such as hydrogen production, photosynthesis, and cellular respiration. Electron transfer in living organisms is analogous to an electrical current that powers a household appliance in that there must be a source of electrons (an outlet) and a pathway for the current to follow in order to supply energy to the electrical device so that it can function. The ability to understand and control the biological machinery ? i.e., the source and pathways ? involved in the process of electron-transfer will allow bioengineers to develop microscopic electronic devices that can be used to benefit society.
The PI will establish and interdisciplinary program that is complementary to this research initiative, while promoting diversity and increasing the involvement of underrepresented groups in biological engineering and science .
Designing Electron-Transfer Proteins Corey J. Wilson – Yale University Simplified Description Outcome or Accomplishment: A research group at Yale University is developing rational design rules for protein based charge transfer. Impact: Our ability to produce viable bioelectronics will advance our understanding of fundamental life processes and expand the use of designed biomolecules as the building blocks of higher-level functional devices such as: biomaterial-based electronic circuitry and biofuel cells that use natural substances in the body to generate energy to power implantable devices. Background the lay reader needs to understand the significance of this outcome: Life is inextricably linked to a process called electron-transfer (ET). ET reactions are central to bioenergetic processes, such as hydrogen production, photosynthesis, and cellular respiration. ET in living organisms is analogous to an electrical current that powers a household appliance in that there must be a source of electrons (an outlet) and a pathway for the current to follow in order to supply energy to the electrical device so that it can function. Our ability to understand and control the biological machinery – i.e., the source and pathways – involved in the process of electron-transfer will allow us to develop microscopic electronic devices that can be used to benefit society. Detailed Engineering Description Background: Single electron-transfer reactions give rise to most biological oxidation–reduction (redox) processes. These rather simple chemical transformations require specialized protein systems. Nature preferentially employs metalloproteins for ET, because the reduction potentials of metal-ions are more easily tunable than those of organic compounds. From an engineering vantage point, the challenge is how to translate our existing knowledge with regard to biological ET into a robust design strategy. Results: Wilson et al. has developed a robust design cycle that enable researches to: (i) systematically ideate a specific charge-transfer event, (ii) rationally model the system using a theory inspired algorithm, and (iii) experimentally test the system in a way that provides real-time feedback to the modeling procedure. The ET modeling procedure is based on a standard protein design force-field, with additional terms to account for explicit charge-transfer properties in a given protein scaffold. To validate designs, ET analogs are experimentally characterized using a combination of chemical, biochemical and biophysical methods. New experimental knowledge is then used to improve the design procedure. The impact of this study is two-fold: (i) this procedure will facilitate the development of not simply novel but useful charge-transfer devices that will benefit society; (ii) in light of a number of unknowns with regard to biological ET, a secondary benefit of this study is that it provides a systematic strategy for generating and rigorously testing interesting unanswered questions with regard to biological ET. To date we have benchmarked the model system Pseudomonas aeruginosa azurin introducing a new mechanism for coupling between electron acceptor and donor sites, thus developing the experimental methods needed to validate any new designs (Tobin and Wilson, 2014, JACS, doi: 10.1021/ja412308r). We have completed a major protein design study for electronic coupling, which involves a complete design cycle (computational design, electro-chemistry, EPR, photochemistry, and crystallography) (Tobin et al. 2014 (in preparation)). In this study, we also solved the atomic-structures for 6 of the 8 designs (PDB IDs: 4KO9, 4KOC, 4KO5, 4KO6, 4KO7, 4KOB). In addition, Wilson et al. have developed an innovative / novel multistate design strategy that will improve the design if ET systems (Howell et al. 2014, Structure doi: 10.1016/j.str.2013.10.019). Broader Impacts: Wilson was the Keynote Speaker at the Inaugural Biomolecular Engineering Symposium, during the 3rd Annual Masters Biotechnology Program Open House at Claflin University (a Historically Black College). Scientific Uniqueness: This research idea and approach is transformative, in that this study engages and integrates multiple disciplines culminating in a novel approach for translating our knowledge with regard to general electron-transfer from an interpolative science to an extrapolative engineering methodology.