Collaborative Research: De Novo Protein Constructs for Photosynthetic Energy Transduction

About This Grant

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professors Michael Therien and David Beratan of Duke University and William DeGrado of University of California San Francisco are studying new approaches to design materials that direct, store, and release energy. Biology has developed numerous designs that carry out these functions; chemists, however, have yet to create energy harvesting, storage, and release systems from scratch that possess the sophistication of those seen in nature. Recent advances in protein design enable chemists to construct large molecules that capture and manage the flow of positive charges, negative charges, and energy. By designing protein-based materials that migrate and collect charges and energy, unique optical, electrical, and chemical functions will be realized. The experimental procedures used in this effort provide new tools to build proteins having innovative designed functions. This pursuit allow graduate students and postdoctoral fellows to acquire specialized training in synthetic chemistry, protein design, protein biochemistry, modern computational methods, and techniques to monitor fast processes that move charge and energy. The protein design methods developed are broadly applicable and enable construction of new biologically inspired materials that carry out novel functions not seen in nature. Outreach activities of this project introduce college and pre-college students to important new technologies and teach skills important for future careers in science and engineering. Biological energy transduction relies on protein-cofactor assemblies that possess physico-chemical functionality that far exceeds that realized to date through molecular and macromolecular design and synthesis. This effort designs redox proteins that transduce energy using bound cofactors, redox-active amino acids, titratable sidechains, and buried water molecules, to orchestrate the light-triggered flow of electrons, holes, and protons, elucidating rules and principles important for driving thermodynamically reversible reactions at low overpotential and engineering vectorial control over electron and proton currents. This project takes advantage of an integrated, multi-disciplinary approach that employs: (i) design and synthesis of light-harvesting and redox-active cofactors, (ii) de novo protein design using advanced computational methods to selectively bind cofactor units in precise, organized spatial arrangements, (iii) protein expression and characterization, (iv) state-of-the-art pump-probe transient optical methods and theoretical models that interrogate photo-induced electron and proton migration reactions, and (v) spectroscopic, potentiometric, and dynamical methods, high resolution protein structure, and predictions made by theory to provide insights into how atomic-level control of cofactor environments directs energy transducing function. Information from this study elucidate fundamental principles required to understand photosynthetic energy transduction and to design proteins that possess novel electro-optic function and can transduce energy via innovative pathways. 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.