Conformational Motion of Enzymes Studied by Evanescent Wave Microscopy

用倏逝波显微镜研究酶的构象运动

• 批准号: 0105903
• 负责人: Giovanni Zocchi
• 金额: $ 27万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2003-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0105903&HistoricalAwards=false
• 关键词: Conformational; Motion; Enzymes; Studied; Evanescent

This individual investigator award provides support to an assistant professor for a project working at the physics/biology interface. The project investigates conformational motion of biological macromolecules which is coupled to substrate recognition and enzymatic catalysis. This mechano-chemical aspect is crucial in two ways: it ensures the high specificity of enzymatic reactions and it produces the ordered motion at the molecular scale by which the cell's devices operate (channels, motors, receptors). The study develops and applies a micro-mechanical technique which allows the detection of conformational changes of single proteins or DNA oligonucleotides and at the same time applies a controlled force to the molecule. It is an extension of earlier methods that were successfully applied to motor proteins, and it will allow the study a broader class of enzymes. The object is to gain insight into the physical principles under which these molecular devices operate; eventually this will generate design criteria for artificial molecular devices. The project provides excellent opportunities for training graduate students in this fast growing interdisciplinary field. Students will learn to use and develop state-of-the-art molecular biophysics techniques, such as single molecule detection and manipulation, nanomechanics, optical tweezers. This know-how is presently much in demand both in academics and the biotechnology industry. %%%This individual investigator award provides support to an assistant professor for a project working at the physics/biology interface. The project focuses on one of the distinctive characteristics of biological macromolecules (proteins, DNA): their ability to change shape in response to an external (chemical) stimulus. This is the bases for nature's molecular devices in the cell, and it will form the basis of operation of artificial molecular sensors and actuators in the future. The project develops a single molecule micro-mechanical technique to study these conformational changes from the point of view of the physical principles underlying such molecular machines. Students participating in the project will acquire experience in an array of state-of-the-art molecular biophysics techniques, such as near field optics, nanomechanics, optical tweezers. Being able to participate in all aspects of the experiments, from design to implementation to analysis, students will acquire the ability to devise original solutions to technical challenges. Such background in the interdisciplinary field of biophysics is at present much sought after both in academics and the biotechnology industry. ***

该个人研究者奖为在物理/生物界面工作的助理教授提供项目支持。该项目研究了与底物识别和酶催化相结合的生物大分子的构象运动。这种机械化学方面在两个方面至关重要：它确保酶促反应的高特异性，并在分子尺度上产生细胞设备（通道，马达，受体）运行的有序运动。该研究开发并应用了一种微机械技术，该技术可以检测单个蛋白质或DNA寡核苷酸的构象变化，同时对分子施加控制力。这是早期成功应用于运动蛋白的方法的延伸，它将使研究更广泛的酶类成为可能。目的是深入了解这些分子装置运作的物理原理；最终，这将产生人造分子装置的设计标准。该项目为在这个快速发展的跨学科领域培养研究生提供了极好的机会。学生将学习使用和开发最先进的分子生物物理学技术，如单分子检测和操作，纳米力学，光学镊子。这种技术目前在学术界和生物技术行业都很有需求。该个人研究者奖为在物理/生物学界面工作的助理教授提供项目支持。该项目聚焦于生物大分子（蛋白质、DNA）的一个显著特征：它们响应外部（化学）刺激而改变形状的能力。这是自然界分子装置在细胞中的基础，也将构成未来人工分子传感器和致动器的运行基础。该项目开发了一种单分子微机械技术，从这些分子机器背后的物理原理的角度来研究这些构象变化。参与该项目的学生将获得一系列最先进的分子生物物理学技术的经验，如近场光学、纳米力学、光学镊子。能够参与实验的各个方面，从设计到实施再到分析，学生将获得针对技术挑战设计原创解决方案的能力。这种生物物理学跨学科领域的背景目前在学术界和生物技术行业都很受追捧。＊＊＊