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Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling

Nature Methods volume 6, pages 551–552 (2009)Cite this article

To the Editor: Proteins exploit the conformational variability of loop regions to carry out diverse biological tasks including molecular recognition and signal transduction. New algorithms to engineer these functions by combining loop building and sequence design therefore have enormous practical applications but require high-resolution 'loop reconstruction': the modeling of protein loop conformations, given the amino acid sequence. Loop reconstruction in protein design may be simplified conceptually by restricting changes to the functional loop regions. However, despite progress in loop prediction methods1,2, design applications are limited by the difficulty in modeling purely local conformational moves and by the need for advances in sampling and evaluating loop conformations.

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Figure 1: Loop reconstruction with KIC.
Figure 2: Performance of the KIC loop reconstruction protocol.

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Acknowledgements

We thank D. Baker and A. Sali for valuable comments, and B. Sellers and M. Jacobson for sharing data and for helpful discussions. This work was supported by grants from the US National Institutes of Health to T.K. (PN2-EY016525) and E.A.C (R01-GM08171), the University of California Lab Research Program (T.K.), and a PhRMA Foundation Predoctoral Fellowship (D.J.M.).

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Authors and Affiliations

  1. Graduate Program in Bioinformatics and Computational Biology,

    Daniel J Mandell & Tanja Kortemme

  2. California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California, USA

    Daniel J Mandell & Tanja Kortemme

  3. Department of Mathematics and Statistics, University of New Mexico, Albuquerque, New Mexico, USA

    Evangelos A Coutsias

  4. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA

    Tanja Kortemme

Authors
  1. Daniel J Mandell
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  2. Evangelos A Coutsias
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  3. Tanja Kortemme
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Corresponding author

Correspondence to Tanja Kortemme.

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Supplementary Figures 1–4, Supplementary Tables 1–8, Supplementary Methods, Supplementary Discussion (PDF 3700 kb)

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Mandell, D., Coutsias, E. & Kortemme, T. Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. Nat Methods 6, 551–552 (2009). https://doi.org/10.1038/nmeth0809-551

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