Collaborative Research: De novo Protein Constructs for Photosynthetic Energy Transduction

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

This project is jointly funded by the Chemistry of Life Processes Program in the Division of Chemistry, the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, and the Physics of Living Systems in the Division of Physics. With this award, the three investigators, Dr. Michael J. Therien (Duke University), Dr. William F. DeGrado (University of California at San Francisco), and Dr. Jeffery G. Saven (University of Pennsylvania) are investigating new approaches to design proteins that collect, store, and release energy. Scientists are not yet able to mimic biology in creating protein-based energy harvesting, storage, and release systems. Recent advances in protein design enable chemists to construct large molecules that can capture and direct the flow of charge and energy. The experimental procedures used in this effort (i) provide new tools to build proteins having novel designed functions, and (ii) characterize the structures and energy storage and release functions of these proteins. This research trains graduate students and postdoctoral fellows in synthetic chemistry, protein design, protein biochemistry, and modern computational methods. The students and fellows are also trained in techniques to monitor fast processes that move charge and energy, especially related to solar energy conversion. The protein design methods developed are broadly applicable. They enable construction of new biologically-inspired systems that carry out novel functions not seen in nature. Outreach activities of this project introduce college and pre-college students to important new technologies. These activities also teach skills important for future careers in science and engineering. Biological energy transduction relies on protein-cofactor assemblies that possess physico-chemical complexity that far exceeds that realized to date through molecular, supramolecular, and macromolecular design and synthesis. This research project is undertaken to realize such complexity through "design from scratch" strategies that exploit de novo proteins. These de novo proteins bind abiological cofactors and elucidate fundamental design principles required for photosynthetic energy harvesting, storage, and release. This project takes advantage of an integrated, multi-disciplinary approach to evolve peptide-cofactor complexes that possess sophisticated electro-optic functionality. Such functionality encompasses cofactor design and synthesis, advanced computational methods, protein expression and characterization and state-of-the-art pump-probe transient optical methods. The computational methods allow the design of proteins that bind co-factors in a precisely organized spatial arrangement. State-of-the-art, pump-probe, transient optical methods characterize function and reaction dynamics. Information from this study elucidates fundamental principles required for photosynthetic energy transduction, and provide general strategies to interrogate important protein structure-function relationships.