Experimental and Theoretical Studies of Charge-Charge Interactions in Proteins

蛋白质中电荷相互作用的实验和理论研究

• 批准号: 1330249
• 负责人: George Makhatadze
• 金额: $ 117.86万
• 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: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1330249&HistoricalAwards=false
• 关键词: Experimental; Theoretical; Studies; Charge; Interactions

The major goal of this research project, jointly funded by Molecular Biophysics in the Division of MCB and Physics of Living Systems Program in the Division of Physics, is to understand the role of charge-charge interactions in determining the thermodynamic stability of proteins and modulation of the folding energy landscape. It relies on the synergy between computer simulations and experiments. This study will test the hypothesis that charge-charge interactions on the protein surface are important determinants of the folding energy landscape. Approaches developed during the previous funding cycle significantly advanced the ability to predict the effects of surface charge-charge interactions on protein stability and provided an important tool that allows the combination of computer simulations, inspired by the energy landscape theory, with experimental measurements of the rates for protein folding/unfolding. Specific questions that will be addressed are: What is the role of charge-charge interactions in shaping the folding energy landscape? What is the effect that electrostatic interactions have on defining the protein kinetic stability? What is the role of salt-bridges in defining the stability of collagen molecule? The PI is actively involved in curriculum development and serves as an Undergraduate curriculum adviser for Biochemistry and Biophysics majors at RPI. In addition he engages high school, undergraduate and graduate students in both computational and experimental aspects of research in his laboratory. Over 50% of trainees are females or members of underrepresented minorities. The majority of the high-school and undergraduate students who were trained in the lab continue their education in STEM disciplines. The research will provide a systematic study of the mechanism of protein stabilization by charge-charge interactions by uniquely combining a variety of biochemical, biophysical and computational tools. As such, it is expected that the knowledge accumulated as a result of these experiments will lay the foundation to future studies of these fundamentally important issues with broad implications for many different areas of biotechnology that use proteins including development of next generation of biosensors, environmentally friendly catalysts and robust biomaterials.

该研究项目由 MCB 部门的分子生物物理学和物理部门的生命系统物理学项目联合资助，其主要目标是了解电荷-电荷相互作用在确定蛋白质的热力学稳定性和调节折叠能源景观。 它依赖于计算机模拟和实验之间的协同作用。 这项研究将检验以下假设：蛋白质表面上的电荷相互作用是折叠能量景观的重要决定因素。 在上一个资助周期中开发的方法显着提高了预测表面电荷-电荷相互作用对蛋白质稳定性影响的能力，并提供了一个重要的工具，可以将受能源景观理论启发的计算机模拟与速率的实验测量相结合用于蛋白质折叠/解折叠。 将解决的具体问题是：电荷-电荷相互作用在塑造折叠能量景观中的作用是什么？ 静电相互作用对定义蛋白质动力学稳定性有什么影响？ 盐桥在决定胶原蛋白分子的稳定性方面起什么作用？ PI 积极参与课程开发，并担任 RPI 生物化学和生物物理学专业的本科课程顾问。 此外，他还让高中生、本科生和研究生在他的实验室进行计算和实验方面的研究。 超过 50% 的学员是女性或代表性不足的少数族裔成员。 大多数在实验室接受培训的高中生和本科生继续接受 STEM 学科的教育。 该研究将通过独特地结合各种生物化学、生物物理和计算工具，对电荷-电荷相互作用稳定蛋白质的机制进行系统研究。 因此，预计这些实验所积累的知识将为这些根本性重要问题的未来研究奠定基础，这些问题对使用蛋白质的生物技术的许多不同领域具有广泛的影响，包括开发下一代生物传感器、环境友好型生物传感器和生物传感器。催化剂和坚固的生物材料。