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A general Monte Carlo/simulated annealing algorithm for resonance assignment in NMR of uniformly labeled biopolymers

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Abstract

We describe a general computational approach to site-specific resonance assignments in multidimensional NMR studies of uniformly 15N,13C-labeled biopolymers, based on a simple Monte Carlo/simulated annealing (MCSA) algorithm contained in the program MCASSIGN2. Input to MCASSIGN2 includes lists of multidimensional signals in the NMR spectra with their possible residue-type assignments (which need not be unique), the biopolymer sequence, and a table that describes the connections that relate one signal list to another. As output, MCASSIGN2 produces a high-scoring sequential assignment of the multidimensional signals, using a score function that rewards good connections (i.e., agreement between relevant sets of chemical shifts in different signal lists) and penalizes bad connections, unassigned signals, and assignment gaps. Examination of a set of high-scoring assignments from a large number of independent runs allows one to determine whether a unique assignment exists for the entire sequence or parts thereof. We demonstrate the MCSA algorithm using two-dimensional (2D) and three-dimensional (3D) solid state NMR spectra of several model protein samples (α-spectrin SH3 domain and protein G/B1 microcrystals, HET-s218–289 fibrils), obtained with magic-angle spinning and standard polarization transfer techniques. The MCSA algorithm and MCASSIGN2 program can accommodate arbitrary combinations of NMR spectra with arbitrary dimensionality, and can therefore be applied in many areas of solid state and solution NMR.

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Acknowledgments

This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases within the National Institutes of Health. Computational facilities of the Helix Systems at the National Institutes of Health were used in this work.

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Authors and Affiliations

  1. Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 112, Bethesda, MD, 20892-0520, USA

    Kan-Nian Hu, Wei Qiang & Robert Tycko

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  1. Kan-Nian Hu
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  2. Wei Qiang
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  3. Robert Tycko
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Correspondence to Robert Tycko.

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Hu, KN., Qiang, W. & Tycko, R. A general Monte Carlo/simulated annealing algorithm for resonance assignment in NMR of uniformly labeled biopolymers. J Biomol NMR 50, 267–276 (2011). https://doi.org/10.1007/s10858-011-9517-1

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