Simulation for design and engineering of de novo redox proteins

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This project will apply a range of computational molecular simulation methods to contribute to design, engineering and understanding of construction of single and multicentre redox and chromophore proteins. This work will be carried out in close collaboration with experiments. Overall, this will not only address deficiencies in fundamental knowledge but also provide powerful routes to harnessing and exploiting the exceptional functional properties of natural proteins, such as efficient photon capture and energy transduction, long range and directional electron transfer, multi-electron redox catalysis, and transmembrane proton translocation for generating proton motive force. We will use state-of-the-art computational methods to design multi-centre soluble and membrane proteins with defined biophysical and dynamic properties, with designed ability to bind specific cofactors. Subsequently, these proteins will form the building blocks for more sophisticated architectures, ultimately aiming to contribute to the development of nanoscale molecular wires for directionally defined electron transfer, artificial yet biocompatible respiratory complexes, soluble and membrane-bound assemblies for broadband light harvesting, and photocatalytic enzymes for multi-electron catalysis. Central to this proposed work will be the implementation of our computational design and analysis pipeline, including within a virtual reality environment, and collaboration with state-of-the-art spectroscopy to map energy and electron transfer within the designed proteins and assemblies, applying quantum mechanical and multiscale methods to calculate electronic properties. This will link to time-resolved multidimensional and ultrafast spectroscopic experiments to probe energy and electron transfer processes within multi-centre de novo proteins and enzymes from microsecond to femtosecond timescales. Overall, this project will contribute to developing a comprehensive in silico pipeline for redox enzyme design and engineering, leading to soluble, modular multi-centre redox proteins and enzymes for long-range electron transfer, electron bifurcation, catalysis, broadband light harvesting and energy transfer.