Enzymes catalyze chemical reactions that are essential for industrial applications, energy conversion processes, and life. A better understanding of how enzymes perform these chemical reactions will have a major impact on a large number of scientific disciplines. In particular, deeper insight into how enzymes change their three-dimensional shape is essential to this understanding, yet in even the best characterized enzymes, the fundamental details of their molecular motions remain only crudely understood. In this project, these motions will be characterized and their role in enzyme catalytic function will be elucidated by a powerful combination of experimental and computational techniques. These experiments will be applied to the model enzyme, triosephosphate isomerase (TIM) and will not only provide a better understanding of TIM enzyme function, but will also provide important information about enzymes in general that will aid research in a myriad of related scientific fields.

The objectives of this research are to perform outstanding science on important problems and to train young scientists to attack this and other scientific problems from a variety of experimental perspectives and furthermore, to challenge them to arrive at creative solutions. This goal will be accomplished through three approaches. (a) Teaching. Students will be educated in fundamental biophysical concepts through traditional coursework that includes detailed study of relevant scientific literature. (b) Research Mentoring. Undergraduate and graduate students will be mentored in scientific research. A particular emphasis of this project focuses on recruiting undergraduates from geographically underrepresented, rural Appalachia to participate in this research project. By including students from geographically underrepresented areas this project will enhance their educational experience and expand the training for those who would not normally have such opportunities. (c) Facilitating Group Interaction. Often, scientific problems require multiple approaches to achieve a solution. To encourage students to integrate results obtained from multiple experiments, this research project will promote interactions among students with diverse research backgrounds. To this end, weekly joint group meetings with research groups that focus on computational methods will be held.

National Science Foundation (NSF)
Division of Molecular and Cellular Biosciences (MCB)
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Kamal Shukla
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Yale University
New Haven
United States
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