CAREER: Dynamics of Computationally Designed Fluorescent Proteins

职业：计算设计的荧光蛋白的动力学

• 批准号: 2144396
• 负责人: Colin Smith
• 金额: $ 99.67万
• 依托单位: Wesleyan University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2144396&HistoricalAwards=false
• 关键词: CAREER; Dynamics; Computationally; Designed; Fluorescent

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). The design of proteins with novel activity, behavior, or purpose has been an important area of research. The field of computational protein design is becoming increasingly sophisticated, enabling not only the redesign of existing proteins but also the creation of proteins entirely from scratch. The goal of this project is to study and optimize the movement of microscopic, computationally designed proteins that use light to track the locations of biological molecules and reveal the inner working of living organisms. This will enable the creation of even more advanced versions of these and other protein machines that can also help in the manufacture and recycling of materials at the chemical level. The project will employ several graduate and undergraduate students in full-time research, preparing them for careers where computational and experimental methods are increasingly integrated to solve the next set of major scientific challenges. This work will support a suite of new class-based research projects, empowering undergraduates in scientific discovery and advancing knowledge. Students from backgrounds underrepresented in science, technology, engineering, and mathematics will be reached through established programs assisting the transition to college and preparation for graduate school. American Rescue Plan funding is used to support this early career investigator at a critical stage in his career.While the structure of a protein is almost always necessary for function, it is often not sufficient. This project focuses on the critical but often neglected role of protein motion in enabling absorbance and reemission of light, a process known as fluorescence. We will first determine which protein shapes either enhance or inhibit fluorescence through detailed analysis of computer simulations and extensive experimental structural characterization. Second, we will test our models through redesign and experimental examination of brighter fluorescent protein variants. As part of these efforts, we will develop a general-purpose computer algorithm that enables rapid evaluation of how thousands of potential mutations affect the shape of the protein. Third, we will investigate the structural determinants of other important properties like the ability of the protein to prevent or facilitate switching fluorescence on and off. Ultimately, this project aims to develop a detailed understanding of how these fluorescent proteins and others can be redesigned to make them truly useful tools for biological research and industrial processes.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.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。具有新型活性，行为或目的的蛋白质的设计一直是研究的重要领域。计算蛋白设计领域越来越复杂，不仅可以重新设计现有蛋白质，而且还可以完全从头开始创建蛋白质。该项目的目的是研究和优化微观，计算设计的蛋白质的运动，这些蛋白质使用光来跟踪生物分子的位置并揭示生物体的内部工作。这将使这些和其他蛋白质机器的更先进的版本也可以帮助化学水平的材料的生产和回收。该项目将在全日制研究中聘请几名研究生和本科生，为他们做好准备，即越来越多地整合计算和实验方法以解决下一系列重大科学挑战的职业。这项工作将支持一套新的基于班级的研究项目，从而赋予科学发现和进步知识的大学生能力。来自科学，技术，工程和数学的人数不足的学生将通过有助于过渡到大学并为研究生院做准备的既定计划来联系。美国的救援计划资金用于在职业生涯的关键阶段为这位早期职业调查员提供支持。虽然蛋白质的结构几乎总是需要用于功能的必要条件，但通常不够。该项目着重于蛋白质运动在使光的吸光度和重新排放中的关键但经常被忽略的作用，这是一种称为荧光的过程。我们将首先通过详细分析计算机模拟和广泛的实验结构表征来确定哪种蛋白质形状可以增强或抑制荧光。其次，我们将通过重新设计和实验检查更明亮的荧光蛋白质变体来测试我们的模型。作为这些努力的一部分，我们将开发一种通用计算机算法，该算法能够快速评估数千种潜在突变如何影响蛋白质的形状。第三，我们将研究其他重要特性的结构决定因素，例如蛋白质预防或促进开关荧光的能力。最终，该项目旨在对如何重新设计这些荧光蛋白和其他项目的详细了解，以使其成为生物学研究和工业流程的真正有用的工具。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。