Cited by 88Protein Structure and Dynamicsvaccines and immunoinformatics approachesMonoclonal and Polyclonal Antibodies Research

Antibody i-Patch prediction of the antibody binding site improves rigid local antibody–antigen docking

Krawczyk, K., Baker, T., Shi, J., Deane, C. M.·2013·Protein Engineering Design and Selection

Abstract

Antibodies are a class of proteins indispensable for the vertebrate immune system. The general architecture of all antibodies is very similar, but they contain a hypervariable region which allows millions of antibody variants to exist, each of which can bind to different molecules. This binding malleability means that antibodies are an increasingly important category of biopharmaceuticals and biomarkers. We present Antibody i-Patch, a method that annotates the most likely antibody residues to be in contact with the antigen. We show that our predictions correlate with energetic importance and thus we argue that they may be useful in guiding mutations in the artificial affinity maturation process. Using our predictions as constraints for a rigid-body docking algorithm, we are able to obtain high-quality results in minutes. Our annotation method and re-scoring system for docking achieve their predictive power by using antibody-specific statistics. Antibody i-Patch is available from http://www.stats.ox.ac.uk/research/proteins/resources.

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  • Modelled antibody structures can be used at the Lead Identification stage to select surface exposed paratope residues for mutations or to characterize binding with respect to the cognate epitope.

    “Modelled structures can be used at the Lead Identification stage to select surface exposed paratope residues for mutations [110] or to characterize the binding with respect to the cognate epitope [119].”
  • Antibody i-Patch assigns a score to each residue with respect to its propensity to be part of the paratope, with high-scoring residues offering potential candidates for mutagenesis.

    “For instance, statistical approaches such as Antibody i-Patch [110] assign a score to each residue with respect to its propensity to be part of the paratope, with high-scoring residues offering potential candidates for mutagenesis.”

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Authors
Krawczyk, K., Baker, T., Shi, J., & Deane, C. M.
Affiliations
  • University of Oxford (GB)
  • UCB Pharma (United Kingdom) (GB)
  • Chinese Academy of Sciences (CN)
Venue
Protein Engineering Design and Selection
Published
2013-09-04
Volume
26
Issue
10
Pages
621-629
ISSN
  • 0269-2139 (ISSN-L)
  • 1741-0126
  • 1741-0134
OpenAlex
W2117012297
Cited by
87
References
29
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 12 · 2019: 7 · 2018: 13 · 2017: 6 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 1
FWCI
1.49
Type
journal article
Language
en
Open access
closed
Locations
  • Protein Engineering Design and Selection (publishedVersion)
  • PubMed (publishedVersion)
Funders
Engineering and Physical Sciences Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
antibody-antigen docking, rigid-body docking, hypervariable region, affinity maturation, antibody design
MeSH terms
Algorithms, Antibodies, Antigens, Binding Sites, Computational Biology, Complementarity Determining Regions, Molecular Docking Simulation

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