High throughput and quantitative enzymology in the genomic era |
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Institution: | 1. Department of Chemistry, University of Washington, Seattle, WA 98195, USA;1. Harry Perkins Institute of Medical Research, Nedlands, WA, Australia;2. The University of Western Australia Centre for Medical Research, Crawley, WA, Australia;3. School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia;4. School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, Australia;5. Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, Australia |
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Abstract: | Accurate predictions from models based on physical principles are the ultimate metric of our biophysical understanding. Although there has been stunning progress toward structure prediction, quantitative prediction of enzyme function has remained challenging. Realizing this goal will require large numbers of quantitative measurements of rate and binding constants and the use of these ground-truth data sets to guide the development and testing of these quantitative models. Ground truth data more closely linked to the underlying physical forces are also desired. Here, we describe technological advances that enable both types of ground truth measurements. These advances allow classic models to be tested, provide novel mechanistic insights, and place us on the path toward a predictive understanding of enzyme structure and function. |
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