The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Thermodynamic prediction of protein neutrality
Open accessAbstract
We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wild-type structure after one or more random amino acid substitutions. Our theory predicts that for large numbers of substitutions the probability that a protein retains its structure will decline exponentially with the number of substitutions, with the severity of this decline determined by properties of the structure. Our theory also predicts that a protein can gain extra robustness to the first few substitutions by increasing its thermodynamic stability. We validate our theory with simulations on lattice protein models and by showing that it quantitatively predicts previously published experimental measurements on subtilisin and our own measurements on variants of TEM1 β-lactamase. Our work unifies observations about the clustering of functional proteins in sequence space, and provides a basis for interpreting the response of proteins to substitutions in protein engineering applications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Principles that Govern the Folding of Protein Chains
Anfinsen, C. B. (1973) · Science · doi:10.1126/science.181.4096.223 · Cited by 7,096
Guerois, R., Nielsen, J. E., & Serrano, L. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00442-4 · Cited by 1,728
Complete mutagenesis of the HIV-1 protease
Loeb, D. D., Swanstrom, R., Everitt, L., Manchester, M., Stamper, S. E., & Hutchison, C. A. (1989) · Nature · doi:10.1038/340397a0 · Cited by 327
Estimating the prevalence of protein sequences adopting functional enzyme folds
Axe, D. D. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.06.058 · Cited by 86
Cited by
Why highly expressed proteins evolve slowly
Drummond, D. A., Bloom, J. D., Adami, C., Wilke, C. O., & Arnold, F. H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504070102 · Cited by 815
Self-citationEnzyme promiscuity: evolutionary and mechanistic aspects
Khersonsky, O., Roodveldt, C., & Tawfik, D. S. (2006) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2006.08.011 · Cited by 641
The evolutionary consequences of erroneous protein synthesis
Allan Drummond, D., & Wilke, C. O. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2662 · Cited by 515
Self-citationA Comprehensive Biophysical Description of Pairwise Epistasis throughout an Entire Protein Domain
Olson, C. A., Wu, N. C., & Sun, R. (2014) · Current Biology · doi:10.1016/j.cub.2014.09.072 · Cited by 408
Expanding functional protein sequence spaces using generative adversarial networks
Repecka, D., Jauniskis, V., Karpus, L., Rembeza, E., Rokaitis, I., Zrimec, J., Poviloniene, S., Laurynenas, A., Viknander, S., Abuajwa, W., et al. (2021) · Nature Machine Intelligence · doi:10.1038/s42256-021-00310-5 · Cited by 388
Stepwise Modification of a Modular Enhancer Underlies Adaptation in a Drosophila Population
Rebeiz, M., Pool, J. E., Kassner, V. A., Aquadro, C. F., & Carroll, S. B. (2009) · Science · doi:10.1126/science.1178357 · Cited by 249
Porebski, B. T., & Buckle, A. M. (2016) · Protein Engineering Design and Selection · doi:10.1093/protein/gzw015 · Cited by 215
Virus Evolution: Insights from an Experimental Approach
Elena, S. F., & Sanjuán, R. (2007) · Annual Review of Ecology, Evolution, and Systematics · doi:10.1146/annurev.ecolsys.38.091206.095637 · Cited by 131
Evolution favors protein mutational robustness in sufficiently large populations
Bloom, J. D., Lu, Z., Chen, D., Raval, A., Venturelli, O. S., & Arnold, F. H. (2007) · BMC Biology · doi:10.1186/1741-7007-5-29 · Cited by 119
Self-citationPotential role of phenotypic mutations in the evolution of protein expression and stability
Goldsmith, M., & Tawfik, D. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809506106 · Cited by 81
Lethal mutagenesis of bacteria.
Bull, J. J., & Wilke, C. O. (2008) · Genetics · doi:10.1534/genetics.108.091413 · Cited by 48
Self-citationDistribution and molecular evolution of the anti-CRISPR family AcrIF7
Figueroa, W., Cazares, A., Cazares, D., Wu, Y., de la Cruz, A., Welch, M., Kameyama, L., Nobrega, F. L., & Guarneros, G. (2023) · PLOS Biology · doi:10.1371/journal.pbio.3002072 · Cited by 2
Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1
Birgy, A., Roussel, C., Kemble, H., Mullaert, J., Panigoni, K., Chapron, A., Magnan, M., Jacquier, H., Cocco, S., Monasson, R., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-70627-5 · Cited by 2
Yanai, Y., Tsukada, M., Kimura, Y., & Umeno, D. (2025) · ACS Synthetic Biology · doi:10.1021/acssynbio.4c00169 · Cited by 1
Metadata
- Authors
- Bloom, J. D., Silberg, J. J., Wilke, C. O., Drummond, D. A., Adami, C., & Arnold, F. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-01-11
- Volume
- 102
- Issue
- 3
- Pages
- 606-611
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2169546600
- Cited by
- 353
- References
- 4
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
