The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics
Open accessAbstract
The evolution of proteins with novel function is thought to start from precursor proteins that are conformationally heterogeneous. The corresponding genes may be duplicated and then mutated to select and optimize a specific conformation. However, testing this idea has been difficult because of the challenge of quantifying protein flexibility and conformational heterogeneity as a function of evolution. Here, we report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein. This study demonstrates how protein dynamics may be tailored by evolution and has important implications for our understanding of how novel protein functions are evolved.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Controlled evolution of the antifluorescein antibody 4–4-20 localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein.519”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [519]
In the citing paper
“Antibody evolution may constrain conformational heterogeneity by tailoring protein dynamics.519”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [519]
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
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,397
Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. C. (1977) · Journal of Computational Physics · doi:10.1016/0021-9991(77)90098-5 · Cited by 21,430
Principles of Nonlinear Optical Spectroscopy
Mukamel, S. (1995) · Cited by 4,640
Swope, W. C., Andersen, H. C., Berens, P. H., & Wilson, K. R. (1982) · The Journal of Chemical Physics · doi:10.1063/1.442716 · Cited by 4,068
The Energy Landscapes and Motions of Proteins
Frauenfelder, H., Sligar, S. G., & Wolynes, P. G. (1991) · Science · doi:10.1126/science.1749933 · Cited by 3,250
Encyclopedia of Computational Chemistry
(2003) · Wiley eBooks · doi:10.1002/0470845015 · Cited by 2,757
Encyclopedia of Computational Chemistry
Horn, A. H. C., & Lanig, H. (1999) · Journal of Molecular Modeling · doi:10.1007/s0089490050141 · Cited by 2,524
Application of a Theory of Enzyme Specificity to Protein Synthesis.
Koshland, D. (1958) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.44.2.98 · Cited by 2,140
Subpicosecond Measurements of Polar Solvation Dynamics: Coumarin 153 Revisited
Horng, M. L., Gardecki, J. A., Papazyan, A., & Maroncelli, M. (1995) · The Journal of Physical Chemistry · doi:10.1021/j100048a004 · Cited by 2,091
Femtosecond solvation dynamics of water
Jimenez, R., Fleming, G. R., Kumar, P. V., & Maroncelli, M. (1994) · Nature · doi:10.1038/369471a0 · Cited by 1,271
Research works printed but not linked: 1
- PD Hodgkin Immunologist 6, 223–226 (1998).
Cited by
Sorted by citations
Protein promiscuity and its implications for biotechnology
Nobeli, I., Favia, A. D., & Thornton, J. M. (2009) · Nature Biotechnology · doi:10.1038/nbt1519 · Cited by 508
Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436
Computer-aided antibody design
Kuroda, D., Shirai, H., Jacobson, M. P., & Nakamura, H. (2012) · Protein Engineering Design and Selection · doi:10.1093/protein/gzs024 · Cited by 225
Almagro, J. C., & Fransson, J. (2008) · PubMed · doi:10.2741/2786 · Cited by 223
Nitrile groups as vibrational probes of biomolecular structure and dynamics: an overview
Lindquist, B. A., Furse, K. E., & Corcelli, S. A. (2009) · Physical Chemistry Chemical Physics · doi:10.1039/b908588b · Cited by 171
Metadata
- Authors
- Zimmermann, J., Oakman, E. L., Thorpe, I. F., Shi, X., Abbyad, P., Brooks, C. L., Boxer, S. G., & Romesberg, F. E.
- Affiliations
- Departments of *Chemistry and
- University of California San Diego (US)
- Scripps Research Institute (US)
- Stanford University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-09-12
- Volume
- 103
- Issue
- 37
- Pages
- 13722-13727
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1564241
- OpenAlex
- W2132524280
- Cited by
- 116
- References
- 46
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 10 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 6 · 2012: 11
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- antibody evolution, conformational heterogeneity, protein dynamics, combining site, protein flexibility
- MeSH terms
- Animals, Antibodies, Humans, Immunoglobulin Fab Fragments, Mutation, Protein Conformation, Proteins, Evolution, Molecular, Fluorescein, Surface Plasmon Resonance
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
