Skip to main content

Computational Analysis of Antibody Paratopes for Antibody Sequences in Antibody Libraries

  • Protocol
  • First Online:
Computer-Aided Antibody Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2552))

Abstract

To ensure the functionalities of the antibodies in phage-displayed synthetic antibody libraries, we use computational method to evaluate the designs of the antibody libraries. The computational methodologies developed in our lab for designing antibody library provide rich information on the function of the designed antibody sequences—adequate antibody designs for a specific antigen type should have predicted paratopes for the antigen type. This computational assessment of the designed antibody sequences helps eliminate non-functional designs before proceeding to construct the library designs in the wet lab. As such, only reasonable antibody designs are constructed for antibody discoveries.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Kwong PD, Chuang GY, DeKosky BJ, Gindin T, Georgiev IS, Lemmin T, Schramm CA, Sheng Z, Soto C, Yang AS, Mascola JR, Shapiro L (2017) Antibodyomics: bioinformatics technologies for understanding B-cell immunity to HIV-1. Immunol Rev 275(1):108–128. https://doi.org/10.1111/imr.12480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jian JW, Elumalai P, Pitti T, Wu CY, Tsai KC, Chang JY, Peng HP, Yang AS (2016) Predicting ligand binding sites on protein surfaces by 3-dimensional probability density distributions of interacting atoms. PLoS One 11(8):e0160315. https://doi.org/10.1371/journal.pone.0160315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Peng HP, Lee KH, Jian JW, Yang AS (2014) Origins of specificity and affinity in antibody-protein interactions. Proc Natl Acad Sci U S A 111(26):E2656–E2665. https://doi.org/10.1073/pnas.1401131111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mahalingam R, Peng HP, Yang AS (2014) Prediction of fatty acid-binding residues on protein surfaces with three-dimensional probability distributions of interacting atoms. Biophys Chem 192c:10–19. https://doi.org/10.1016/j.bpc.2014.05.002

    Article  CAS  Google Scholar 

  5. Mahalingam R, Peng HP, Yang AS (2014) Prediction of FMN-binding residues with three-dimensional probability distributions of interacting atoms on protein surfaces. J Theor Biol 343:154–161. https://doi.org/10.1016/j.jtbi.2013.10.020

    Article  CAS  PubMed  Google Scholar 

  6. Yu CM, Peng HP, Chen IC, Lee YC, Chen JB, Tsai KC, Chen CT, Chang JY, Yang EW, Hsu PC, Jian JW, Hsu HJ, Chang HJ, Hsu WL, Huang KF, Ma AC, Yang AS (2012) Rationalization and design of the complementarity determining region sequences in an antibody-antigen recognition interface. PLoS One 7(3):e33340. https://doi.org/10.1371/journal.pone.0033340. PONE-D-11-14795 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tsai KC, Jian JW, Yang EW, Hsu PC, Peng HP, Chen CT, Chen JB, Chang JY, Hsu WL, Yang AS (2012) Prediction of carbohydrate binding sites on protein surfaces with 3-dimensional probability density distributions of interacting atoms. PLoS One 7(7):e40846. https://doi.org/10.1371/journal.pone.0040846. PONE-D-11-25241 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chen CT, Peng HP, Jian JW, Tsai KC, Chang JY, Yang EW, Chen JB, Ho SY, Hsu WL, Yang AS (2012) Protein-protein interaction site predictions with three-dimensional probability distributions of interacting atoms on protein surfaces. PLoS One 7(6):e37706. https://doi.org/10.1371/journal.pone.0037706. PONE-D-11-25431 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Peng HP, Yang AS (2007) Modeling protein loops with knowledge-based prediction of sequence-structure alignment. Bioinformatics 23(21):2836–2842

    Article  CAS  PubMed  Google Scholar 

  10. Weitzner BD, Jeliazkov JR, Lyskov S, Marze N, Kuroda D, Frick R, Adolf-Bryfogle J, Biswas N, Dunbrack RL Jr, Gray JJ (2017) Modeling and docking of antibody structures with Rosetta. Nat Protoc 12(2):401–416. https://doi.org/10.1038/nprot.2016.180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Levy ED (2010) A simple definition of structural regions in proteins and its use in analyzing interface evolution. J Mol Biol 403(4):660–670. https://doi.org/10.1016/j.jmb.2010.09.028

    Article  CAS  PubMed  Google Scholar 

  12. Chen CT, Yang EW, Hsu HJ, Sun YK, Hsu WL, Yang AS (2008) Protease substrate site predictors derived from machine learning on multilevel substrate phage display data. Bioinformatics 24(23):2691–2697

    Article  CAS  PubMed  Google Scholar 

  13. Jian JW, Chen HS, Chiu YK, Peng HP, Tung CP, Chen IC, Yu CM, Tsou YL, Kuo WY, Hsu HJ, Yang AS (2019) Effective binding to protein antigens by antibodies from antibody libraries designed with enhanced protein recognition propensities. MAbs 11(2):373–387. https://doi.org/10.1080/19420862.2018.1550320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by Academia Sinica.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hung-Pin Peng or An-Suei Yang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Peng, HP., Yang, AS. (2023). Computational Analysis of Antibody Paratopes for Antibody Sequences in Antibody Libraries. In: Tsumoto, K., Kuroda, D. (eds) Computer-Aided Antibody Design. Methods in Molecular Biology, vol 2552. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2609-2_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2609-2_24

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2608-5

  • Online ISBN: 978-1-0716-2609-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics