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Open Access Database

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

Robert J Pantazes and Costas D Maranas*

Author Affiliations

Chemical Engineering Department, Penn State University, University Park, PA 16802, USA

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BMC Bioinformatics 2013, 14:168  doi:10.1186/1471-2105-14-168

Published: 30 May 2013

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.

Keywords:
Antibody structure prediction; De novo protein design; V-(D)-J recombination; IMGT®