MAPs: A database of modular antibody parts for predicting tertiary structures and designing affinity matured antibodies

Robert J. Pantazes, Costas D. Maranas

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: The de novo design of a novel protein with a particular function remains a formidable challenge with only isolated and hard-to-repeat successes to date. Due to their many structurally conserved features, antibodies are a family of proteins amenable to predictable rational design. Design algorithms must consider the structural diversity of possible naturally occurring antibodies. The human immune system samples this design space (2 1012) by randomly combining variable, diversity, and joining genes in a process known as V-(D)-J recombination.Description: By analyzing structural features found in affinity matured antibodies, a database of Modular Antibody Parts (MAPs) analogous to the variable, diversity, and joining genes has been constructed for the prediction of antibody tertiary structures. The database contains 929 parts constructed from an analysis of 1168 human, humanized, chimeric, and mouse antibody structures and encompasses all currently observed structural diversity of antibodies.Conclusions: The generation of 260 antibody structures shows that the MAPs database can be used to reliably predict antibody tertiary structures with an average all-atom RMSD of 1.9 Å. Using the broadly neutralizing anti-influenza antibody CH65 and anti-HIV antibody 4E10 as examples, promising starting antibodies for affinity maturation are identified and amino acid changes are traced as antibody affinity maturation occurs.

Original languageEnglish (US)
Article number168
JournalBMC bioinformatics
Volume14
DOIs
StatePublished - May 30 2013

Fingerprint

Antibody Affinity
Antibody
Antibodies
Affine transformation
Databases
Anti-Idiotypic Antibodies
Antibody Diversity
V(D)J Recombination
Joining
HIV Antibodies
Genes
Neutralizing Antibodies
Human Influenza
Immune System
Proteins
Gene
Protein
Immune system
Amino Acids
Influenza

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics
  • Structural Biology

Cite this

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abstract = "Background: The de novo design of a novel protein with a particular function remains a formidable challenge with only isolated and hard-to-repeat successes to date. Due to their many structurally conserved features, antibodies are a family of proteins amenable to predictable rational design. Design algorithms must consider the structural diversity of possible naturally occurring antibodies. The human immune system samples this design space (2 1012) by randomly combining variable, diversity, and joining genes in a process known as V-(D)-J recombination.Description: By analyzing structural features found in affinity matured antibodies, a database of Modular Antibody Parts (MAPs) analogous to the variable, diversity, and joining genes has been constructed for the prediction of antibody tertiary structures. The database contains 929 parts constructed from an analysis of 1168 human, humanized, chimeric, and mouse antibody structures and encompasses all currently observed structural diversity of antibodies.Conclusions: The generation of 260 antibody structures shows that the MAPs database can be used to reliably predict antibody tertiary structures with an average all-atom RMSD of 1.9 {\AA}. Using the broadly neutralizing anti-influenza antibody CH65 and anti-HIV antibody 4E10 as examples, promising starting antibodies for affinity maturation are identified and amino acid changes are traced as antibody affinity maturation occurs.",
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MAPs : A database of modular antibody parts for predicting tertiary structures and designing affinity matured antibodies. / Pantazes, Robert J.; Maranas, Costas D.

In: BMC bioinformatics, Vol. 14, 168, 30.05.2013.

Research output: Contribution to journalArticle

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