Simulation for design and engineering of de novo redox proteins

从头氧化还原蛋白的设计和工程模拟

• 批准号: 2894248
• 金额: --
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2894248
• 关键词: Simulation; design; engineering; de; novo

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.

该项目将采用一系列计算分子模拟方法来有助于对单个和多中心氧化还原和发色团蛋白的构建的设计，工程和理解。这项工作将与实验密切合作进行。总体而言，这不仅将解决基本知识中的缺陷，而且还提供了利用和利用自然蛋白质的非凡功能特性的强大途径，例如有效的光子捕获和能量转导，远距离和方向电子转移，多电子氧化还原催化，以及跨膜蛋白proton proton proton proton odon蛋白蛋白蛋白动力。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，具有结合特定辅助因子的设计能力。 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.这项拟议工作的核心将是我们的计算设计和分析管道的实施，包括在虚拟现实环境中，以及与最先进的光谱合作，以在设计的蛋白质和组件中绘制能量和电子传输，应用量子机械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，以探测从微秒到空秒时尺度的多中心蛋白和酶中的探测能量和电子传递过程。总体而言，该项目将有助于开发用于氧化还原酶设计和工程的硅管道中的全面，从而导致可溶的，模块化的多中心氧化还原蛋白质和酶，用于远程电子传输，电子分叉，催化，催化，宽带光收获和能量转移。