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Recent developments in solution nuclear magnetic resonance (NMR)-based molecular biology

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Abstract

Visualizing post-translational modifications, conformations, and interaction surfaces of protein structures at atomic resolution underpins the development of novel therapeutics to combat disease. As computational resources expand, in silico calculations coupled with experimentally derived structures and functional assays have led to an explosion in structure-based drug design (SBDD) with several compounds in clinical trials. It is increasingly clear that “hidden” transition-state structures along activation trajectories can be harnessed to develop novel classes of allosteric inhibitors. The goal of this mini-review is to empower the clinical researcher with a general knowledge of the strengths and weaknesses of nuclear magnetic resonance (NMR) spectroscopy in molecular medicine. Although NMR can determine protein structures at atomic resolution, its unrivaled strength lies in sensing subtle changes in a nuclei’s chemical environment as a result of intrinsic conformational dynamics, solution conditions, and binding interactions. These can be recorded at atomic resolution, without explicit structure determination, and then incorporated with static structures or molecular dynamics simulations to produce a complete biological picture.

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Acknowledgements

We would like to acknowledge funding from National Institutes of Health grants K99GM115814 (JJZ), and P01 GM047467 and R01 AI037581 (GW), and a Gillian Fellowship from Howard Hughes Medical Institute (DB).

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Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave, Boston, MA, 02115, USA

    Joshua J. Ziarek, Diego Baptista & Gerhard Wagner

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  1. Joshua J. Ziarek
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  2. Diego Baptista
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  3. Gerhard Wagner
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Correspondence to Gerhard Wagner.

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Ziarek, J.J., Baptista, D. & Wagner, G. Recent developments in solution nuclear magnetic resonance (NMR)-based molecular biology. J Mol Med 96, 1–8 (2018). https://doi.org/10.1007/s00109-017-1560-2

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  • DOI: https://doi.org/10.1007/s00109-017-1560-2

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