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MERA: a webserver for evaluating backbone torsion angle distributions in dynamic and disordered proteins from NMR data

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Abstract

MERA (Maximum Entropy Ramachandran map Analysis from NMR data) is a new webserver that generates residue-by-residue Ramachandran map distributions for disordered proteins or disordered regions in proteins on the basis of experimental NMR parameters. As input data, the program currently utilizes up to 12 different parameters. These include three different types of short-range NOEs, three types of backbone chemical shifts (15N, 13Cα, and 13C′), six types of J couplings (3JHNHα, 3JC′C′, 3JC′Hα, 1JHαCα, 2JCαN and 1JCαN), as well as the 15N-relaxation derived J(0) spectral density. The Ramachandran map distributions are reported in terms of populations of their 15° × 15° voxels, and an adjustable maximum entropy weight factor is available to ensure that the obtained distributions will not deviate more from a newly derived coil library distribution than required to account for the experimental data. MERA output includes the agreement between each input parameter and its distribution-derived value. As an application, we demonstrate performance of the program for several residues in the intrinsically disordered protein α-synuclein, as well as for several static and dynamic residues in the folded protein GB3.

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Acknowledgments

This work was supported by the Russian Science Foundation (Grant 14-14-00598) and by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and the Intramural Antiviral Target Program of the Office of the Director, NIH, and by the Max Planck Society. JHL is the recipient of a KVSTA fellowship.

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    Authors and Affiliations

    1. Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, Russian Federation, 119991

      Alexey B. Mantsyzov

    2. Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA

      Yang Shen, Jung Ho Lee & Ad Bax

    3. Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438, Frankfurt am Main, Germany

      Gerhard Hummer

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    1. Alexey B. Mantsyzov
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    2. Yang Shen
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    5. Ad Bax
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    Correspondence to Ad Bax.

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    Alexey B. Mantsyzov and Yang Shen have contributed equally.

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    Mantsyzov, A.B., Shen, Y., Lee, J.H. et al. MERA: a webserver for evaluating backbone torsion angle distributions in dynamic and disordered proteins from NMR data. J Biomol NMR 63, 85–95 (2015). https://doi.org/10.1007/s10858-015-9971-2

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