Evidence map›Paper›PMID 30872635›Full record

ArticleScientific reports2019

Exploring designability of electrostatic complementarity at an antigen-antibody interface directed by mutagenesis, biophysical analysis, and molecular dynamics simulations.

Kouhei Yoshida, Daisuke Kuroda, Masato Kiyoshi, Makoto Nakakido, Satoru Nagatoishi, Shinji Soga, Hiroki Shirai, Kouhei Tsumoto

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Antibody Affinity Maturation by Computational Design.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Theranostic signature of tumor-derived exosomes in cancer.Medical oncology (Northwood, London, England) · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Review
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  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Kouhei YoshidaDepartment of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Daisuke KurodaDepartment of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.ORCID 0000-0003-2390-4785
Masato KiyoshiThe Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.ORCID 0000-0002-5969-8138
Makoto NakakidoDepartment of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Satoru NagatoishiDepartment of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Shinji SogaModality Research Laboratories, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
Hiroki ShiraiModality Research Laboratories, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan.
Kouhei TsumotoDepartment of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. tsumoto@bioeng.t.u-tokyo.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibodies protect organisms from a huge variety of foreign antigens. Antibody diversity originates from both genetic and structural levels. Antigen recognition relies on complementarity between antigen-antibody interfaces. Recent methodological advances in structural biology and the accompanying rapid increase of the number of crystal structures of proteins have enabled atomic-level manipulation of protein structures to effect alterations in function. In this study, we explored the designability of electrostatic complementarity at an antigen-antibody interface on the basis of a crystal structure of the complex. We designed several variants with altered charged residues at the interface and characterized the designed variants by surface plasmon resonance, circular dichroism, differential scanning calorimetry, and molecular dynamics simulations. Both successes and failures of the structure-based design are discussed. The variants that compensate electrostatic interactions can restore the interface complementarity, enabling the cognate antigen-antibody binding. Retrospectively, we also show that these mutational effects could be predicted by the simulations. Our study demonstrates the importance of charged residues on the physical properties of this antigen-antibody interaction and suggests that computational approaches can facilitate design of antibodies that recognize a weakly immunogenic antigen.

Indexed as

MutagenesisAntibodiesAntigen-Antibody ReactionsAntigensCrystallography, X-RayHumansMolecular Dynamics SimulationProtein BindingProtein ConformationRetrospective StudiesStatic ElectricitySurface Plasmon ResonanceAntibodiesAntigens

Identifiers

PMID30872635
PMCPMC6418251

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.