Conformational Motion of Enzymes Studied by Evanescent Wave Microscopy

这个个人研究者奖提供支持，以助理教授在物理学/生物学接口的项目工作。 该项目研究生物大分子的构象运动，它与底物识别和酶催化相结合。这种机械化学方面在两个方面至关重要：它确保了酶反应的高度特异性，并在分子尺度上产生有序的运动，细胞的设备（通道，马达，受体）通过这些运动运行。该研究开发并应用了一种微机械技术，可以检测单个蛋白质或DNA寡核苷酸的构象变化，同时对分子施加受控的力。这是早期成功应用于马达蛋白的方法的延伸，它将允许研究更广泛的酶。其目的是深入了解这些分子器件运行的物理原理;最终这将产生人工分子器件的设计标准。该项目为培养这一快速发展的跨学科领域的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，如单分子检测和操纵，纳米力学，光镊。这种专门知识目前在学术界和生物技术行业都有很大的需求。%这个个人研究者奖提供支持的助理教授在物理/生物学接口的项目工作。 该项目的重点是生物大分子（蛋白质，DNA）的独特特征之一：它们响应外部（化学）刺激而改变形状的能力。这是细胞中自然分子装置的基础，也将成为未来人工分子传感器和致动器的操作基础。该项目开发了一种单分子微机械技术，从这种分子机器的物理原理的角度来研究这些构象变化。参加该项目的学生将获得一系列最先进的分子生物物理技术的经验，如近场光学，纳米力学，光镊。能够参与实验的各个方面，从设计到实施再到分析，学生将获得为技术挑战设计原创解决方案的能力。在生物物理学的跨学科领域的这种背景是目前在学术界和生物技术行业都很抢手。***

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. ***