Conformational Motion of Enzymes Studied by Evanescent Wave Microscopy

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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. ***