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      NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes

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          Abstract

          Allostery is a ubiquitous biological mechanism in which a distant binding site is coupled to and drastically alters the function of a catalytic site in a protein. Allostery provides a high level of spatial and temporal control of the integrity and activity of biomolecular assembles composed of proteins, nucleic acids, or small molecules. Understanding the physical forces that drive allosteric coupling is critical to harnessing this process for use in bioengineering, de novo protein design, and drug discovery. Current microscopic models of allostery highlight the importance of energetics, structural rearrangements, and conformational fluctuations, and in this review, we discuss the synergistic use of solution NMR spectroscopy and computational methods to probe these phenomena in allosteric systems, particularly protein-nucleic acid complexes. This combination of experimental and theoretical techniques facilitates an unparalleled detection of subtle changes to structural and dynamic equilibria in biomolecules with atomic resolution, and we provide a detailed discussion of specialized NMR experiments as well as the complementary methods that provide valuable insight into allosteric pathways in silico. Lastly, we highlight two case studies to demonstrate the adaptability of this approach to enzymes of varying size and mechanistic complexity.

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          Principles of Nuclear Magnetism

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            Protein NMR Spectroscopy. Principles and Practice

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              Author and article information

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              Journal
              Biophysical Reviews
              Biophys Rev
              Springer Science and Business Media LLC
              1867-2450
              1867-2469
              February 2020
              December 14 2019
              February 2020
              : 12
              : 1
              : 155-174
              Article
              10.1007/s12551-019-00609-z
              7040152
              31838649
              ab2fa228-2c5e-403d-83e7-df7be83979a6
              © 2020

              http://www.springer.com/tdm

              http://www.springer.com/tdm

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