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TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts

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Abstract

NMR chemical shifts in proteins depend strongly on local structure. The program TALOS establishes an empirical relation between 13C, 15N and 1H chemical shifts and backbone torsion angles ϕ and ψ (Cornilescu et al. J Biomol NMR 13 289–302, 1999). Extension of the original 20-protein database to 200 proteins increased the fraction of residues for which backbone angles could be predicted from 65 to 74%, while reducing the error rate from 3 to 2.5%. Addition of a two-layer neural network filter to the database fragment selection process forms the basis for a new program, TALOS+, which further enhances the prediction rate to 88.5%, without increasing the error rate. Excluding the 2.5% of residues for which TALOS+ makes predictions that strongly differ from those observed in the crystalline state, the accuracy of predicted ϕ and ψ angles, equals ±13°. Large discrepancies between predictions and crystal structures are primarily limited to loop regions, and for the few cases where multiple X-ray structures are available such residues are often found in different states in the different structures. The TALOS+ output includes predictions for individual residues with missing chemical shifts, and the neural network component of the program also predicts secondary structure with good accuracy.

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Acknowledgments

We thank Alex Grishaev for carrying out the MSG calculation with the new TALOS+ backbone angle restraints. This work was funded by the Intramural Research Program of the NIDDK, NIH. G.C. was supported by NIH grants P41RR02301 (BRTP/NCRR) and P41GM66326 (NIGMS)

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Correspondence to Ad Bax.

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Shen, Y., Delaglio, F., Cornilescu, G. et al. TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR 44, 213–223 (2009). https://doi.org/10.1007/s10858-009-9333-z

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  • DOI: https://doi.org/10.1007/s10858-009-9333-z

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