Molecular Basis of the Effects of Hydrostatic Pressure on Protein Stability

静水压力对蛋白质稳定性影响的分子基础

• 批准号: 1506468
• 负责人: George Makhatadze
• 金额: $ 32.96万
• 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: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1506468&HistoricalAwards=false
• 关键词: Molecular; Basis; Effects; Hydrostatic; Pressure

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor George Makhatadze of Rensselaer Polytechnic Instiute to investigate the role of various physical-chemical interactions in determining the pressure dependence of protein stability. Pressure is an important environmental variable that plays an essential role in biological adaptation for many extremophilic organisms, called barophiles. This research project will rely upon the synergy between computer simulations and experiments. Computer simulations will provide solid theoretical framework for the analysis of the volume changes upon protein unfolding. Experiments will be performed to validate the computer simulations. In particular, these workers will be testing a hypothesis that proteins from barophilic organisms have volumetric properties that allow them to remain folded, even at elevated hydrostatic pressure. This project engages high school, undergraduate and graduate students in both computational and experimental aspects of the research in the laboratory. In recruiting trainees, there will be a particular effort to engage women and/or members of underrepresented minorities. The PI is also actively involved in curriculum development and serves as an undergraduate curriculum adviser for Biochemistry and Biophysics majors at Rensselaer Polytechnic Institute. The proposed work will provide a significant refinement of a protein stability model to incorporate temperature dependencies of volume changes by combining concepts of evolutionary biology with biochemical and biophysical tools such as nuclear magnetic resonance, differential scanning calorimetry as well as computational tools. It is expected that the knowledge accumulated as a result of these experiments will lay the foundation to understand the factors that affect protein folding and stability under extreme conditions. In the longer term, it is hoped that the lessons learned here will provide biophysical chemists with new insights as they seek to design enzymes with that are both active and robust. Broader scientific impacts in industrial biotechnology and in process chemsitry are anticipated, particularly as these scientists seek to develop robust biomaterials and replace current processes with next generation, environmentally friendly catalytic processes.

有了这个奖项，化学过程的化学过程计划是为伦斯勒理工学院的乔治·马赫塔兹（George Makhatadze）教授提供资金，以研究各种物理化学相互作用在确定蛋白质稳定性压力依赖性方面的作用。 压力是一个重要的环境变量，在许多称为男性的极端生物的生物学适应中起着至关重要的作用。 该研究项目将依靠计算机模拟和实验之间的协同作用。 计算机模拟将为分析蛋白质展开时体积变化的分​​析提供坚实的理论框架。 将进行实验以验证计算机模拟。 特别是，这些工人将测试一个假设，即，来自亚肥生物体的蛋白质具有体积特性，即使在静水压力升高下，也可以保持折叠。 该项目与实验室研究的计算和​​实验方面有关高中，本科和研究生。 在招募受训者时，将有一项特殊的努力与妇女和/或代表性不足的少数民族的成员互动。 PI还积极参与课程开发，并担任伦斯勒理工学院生物化学和生物物理专业的本科课程顾问。 拟议的工作将对蛋白质稳定模型进行显着完善，以通过将进化生物学的概念与生物化学和生物物理工具（例如核磁共振，差异扫描量表量热量法以及计算工具）相结合，从而结合体积变化的温度依赖性。 预计由于这些实验而积累的知识将奠定基础，以了解在极端条件下影响蛋白质折叠和稳定性的因素。从长远来看，希望这里学到的经验教训能够为生物物理化学家提供新的见解，因为他们试图设计既活跃又健壮的酶。 预计工业生物技术和过程中的更广泛的科学影响是预计的，特别是当这些科学家寻求开发强大的生物材料并用下一代环保的催化过程替代当前过程时。