Structural Basis of Protein Kinetic Stability

蛋白质动力学稳定性的结构基础

• 批准号: 0519507
• 负责人: Blanca Barquera
• 金额: --
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0519507&HistoricalAwards=false
• 关键词: Structural; Basis; Protein; Kinetic; Stability

Proteins are fascinating macromolecules with unique three-dimensional structures that endow them with diverse life-sustaining functions. Exploiting these functions for applications that could benefit society is limited by various factors, such as the marginal kinetic stability of proteins, which makes them susceptible to degradation. The term "kinetic stability" is used to describe the property of proteins whose structures are trapped in their functional state, and are therefore resistant to degradation. Few proteins in nature are kinetically stable, and unfortunately the chemical and physical basis for this property is poorly understood. The long-term goal of this project is to understand the structural basis of kinetic stability. The project involves the development of a two-dimensional gel electrophoresis assay for the high-throughput detection and quantification of kinetic stability. This novel assay will be used to screen the proteins expressed by various microorganisms and should result in the identification of many kinetically stable proteins. Those proteins emerging from the assay whose three-dimensional structures are known will be used to create a database that will be analyzed using computational approaches to elucidate the structural basis of kinetic stability. An expected outcome of the computational analysis is the generation of an algorithm that can predict whether a protein of known three-dimensional structure possesses kinetic stability. Thus, by revealing how nature has endowed some proteins with high kinetic stability without compromising their function, this project may have a broad impact on society by enabling the rational engineering of proteins. If successful, the knowledge obtained through this project could be applied to improve and expand the use of proteins in many applications, including biomaterials, biosensors, and bioremediation.Broader impact: This project will have an impact on our educational infrastructure by providing training and mentoring to graduate and undergraduate students, including women and underrepresented minorities. Students will work together in an intellectually stimulating environment that integrates mentoring, research training, and learning. Learning through hands-on research is the most effective method for exposing students to science and its career opportunities. Students will work in independent but related research projects that require their frequent interaction and collaboration, and weekly group meetings will provide them a forum to present their research to the other members of the laboratory. Yearly participation at local or national meetings will give students an opportunity to disseminate their results through poster presentations, and will expose them to the broader scientific community and new areas of research.

蛋白质是具有独特三维结构的大分子，具有多种维持生命的功能。将这些功能用于造福社会的应用受到各种因素的限制，例如蛋白质的边际动力学稳定性，这使得它们容易降解。术语“动力学稳定性”用于描述蛋白质的性质，其结构被困在其功能状态中，因此对降解具有抗性。自然界中很少有蛋白质是动力学稳定的，不幸的是，这种性质的化学和物理基础知之甚少。本项目的长期目标是了解动力学稳定性的结构基础。该项目涉及开发用于高通量检测和定量动力学稳定性的二维凝胶电泳分析。这种新的检测方法将用于筛选由各种微生物表达的蛋白质，并应导致许多动力学稳定的蛋白质的鉴定。从测定中出现的那些已知三维结构的蛋白质将用于创建数据库，该数据库将使用计算方法进行分析，以阐明动力学稳定性的结构基础。计算分析的预期结果是生成一种算法，该算法可以预测已知三维结构的蛋白质是否具有动力学稳定性。因此，通过揭示大自然如何赋予某些蛋白质高动力学稳定性而不损害其功能，该项目可能通过实现蛋白质的合理工程而对社会产生广泛的影响。如果成功的话，通过该项目获得的知识可以应用于改善和扩大蛋白质在许多应用中的使用，包括生物材料，生物传感器和生物修复。更广泛的影响：该项目将通过为研究生和本科生提供培训和指导，包括女性和代表性不足的少数民族，对我们的教育基础设施产生影响。学生们将在一个智力刺激的环境中一起工作，整合了指导，研究培训和学习。通过动手研究学习是让学生接触科学及其职业机会的最有效方法。学生将在独立但相关的研究项目中工作，这些项目需要他们频繁的互动和合作，每周的小组会议将为他们提供一个论坛，向实验室的其他成员展示他们的研究。每年参加地方或国家会议将使学生有机会通过海报展示来传播他们的成果，并将使他们接触更广泛的科学界和新的研究领域。