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Eris: an automated estimator of protein stability

Nature Methods volume 4, pages 466–467 (2007)Cite this article

To the editor:

Mutagenesis is a central tool of molecular biology, genetics and biotechnology. To what extent mutations affect the thermodynamic stability (ΔΔG) and structure of a protein is often vital for designing experiments. Estimation of protein stabilities remains a paramount challenge in computational molecular biology and has several bottlenecks. With recent advances in computational biology, accurate ΔΔG calculations can be achieved by molecular dynamic simulations1, but such calculations are computationally costly (that is, efficiency is low). Modern large-scale ΔΔG prediction methods use heuristic algorithms with effective force fields and empirical parameters to estimate the stability changes caused by mutations in agreement with experimental data2,3,4,5. There are, however, two considerable drawbacks pertinent to the heuristic methods. First, most of these prediction methods rely on parameter training using available experimental ΔΔG data. Such training is usually biased toward mutations that feature large-to-small residue substitutions, such as alanine-scanning experiments (that is, poor transferability). Second, protein backbone flexibility, which is crucial for resolving atomic clashes and backbone strains in mutant proteins, is not considered in these methods, thereby reducing accuracy and limiting the application of heuristic methods (that is, limited applicability).

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Figure 1: Performance of Eris.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, USA

    Shuangye Yin, Feng Ding & Nikolay V Dokholyan

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  1. Shuangye Yin
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  2. Feng Ding
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  3. Nikolay V Dokholyan
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Supplementary information

Supplementary Fig. 1

Comparison of Eris ΔΔG calculations with those from other servers. (PDF 87 kb)

Supplementary Table 1

List of the Δn1 > 0 class mutants, the relative solvent accessibilities (RSA) of the mutated residues, the experimental measured ΔΔG, and the evaluated ΔΔG values by various servers. (PDF 75 kb)

Supplementary Table 2

Eris-aided structure pre-relaxation relieves backbone strains of the α-spectrin initial structure. (PDF 36 kb)

Supplementary Methods (PDF 97 kb)

Supplementary Discussion (PDF 149 kb)

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Yin, S., Ding, F. & Dokholyan, N. Eris: an automated estimator of protein stability. Nat Methods 4, 466–467 (2007). https://doi.org/10.1038/nmeth0607-466

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