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.

该项目将应用一系列计算分子模拟方法，以帮助设计、工程和理解单中心和多中心氧化还原和发色团蛋白质的结构。这项工作将与实验密切合作进行。总体而言，这不仅将解决基础知识的不足，而且还将为利用和利用天然蛋白质的特殊功能特性提供强有力的途径，如高效的光子捕获和能量转导、远程和定向电子转移、多电子氧化还原催化以及用于产生质子动力的跨膜质子转移。我们将使用最先进的计算方法来设计具有明确生物物理和动力学性质的多中心可溶蛋白和膜蛋白，并设计出结合特定辅因子的能力。随后，这些蛋白质将形成更复杂的结构的基石，最终目标是促进用于定向电子转移的纳米级分子导线、人工但生物相容的呼吸复合体、用于宽带光捕获的可溶性和膜结合组件以及用于多电子催化的光催化酶的发展。这项拟议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，绘制设计的蛋白质和组件内的能量和电子转移图，应用量子力学和多尺度方法计算电子性质。这将与时间分辨多维和超快光谱实验联系起来，以探测从微秒到飞秒时间尺度的多中心从头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用于氧化还原酶设计和工程的全面的硅胶管道，从而产生可溶的、模块化的多中心氧化还原蛋白质和酶，用于远程电子转移、电子分叉、催化、宽带光收集和能量转移。