Simulation for design and engineering of de novo redox proteins

该项目将应用一系列计算分子模拟方法来帮助设计、工程和理解单中心和多中心氧化还原和发色团蛋白的构建。这项工作将与实验密切合作进行。总的来说，这不仅将解决基础知识的不足，而且还将为利用和开发天然蛋白质的特殊功能特性提供强大的途径，例如有效的光子捕获和能量转导，远距离和定向电子转移，多电子氧化还原催化以及产生质子动力的跨膜质子易位。我们将使用最先进的计算方法来设计具有定义的生物物理和动态特性的多中心可溶性和膜蛋白，并具有结合特定辅因子的设计能力。随后，这些蛋白质将构成更复杂结构的基石，最终旨在促进纳米级分子线的发展，用于定向电子转移，人工但具有生物相容性的呼吸复合物，用于宽带光收集的可溶性和膜结合组件，以及用于多电子催化的光催化酶。这项工作的核心将是实施我们的计算设计和分析管道，包括在虚拟现实环境中，并与最先进的光谱学合作，在设计的蛋白质和组件中绘制能量和电子转移图，应用量子力学和多尺度方法来计算电子特性。这将与时间分辨的多维和超快光谱实验联系起来，以从微秒到飞秒的时间尺度探测多中心新生蛋白质和酶内的能量和电子转移过程。总体而言，该项目将有助于开发一个全面的硅管道氧化还原酶的设计和工程，导致可溶性，模块化多中心氧化还原蛋白和酶的远程电子转移，电子分叉，催化，宽带光收集和能量转移。

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.