Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces
Antibodies have the remarkable ability to recognise their cognate antigens with extraordinary affinity and specificity. Discerning the rules that define antibody-antigen recognition is a fundamental step in the rational design and engineering of functional antibodies with desired properties. In this...
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doaj-70b9c33bd8eb421a8ca2a491f4184dab2021-09-30T04:35:19ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-09-01810.3389/fmolb.2021.749784749784Quantitative Description of Surface Complementarity of Antibody-Antigen InterfacesLorenzo Di Rienzo0Edoardo Milanetti1Edoardo Milanetti2Giancarlo Ruocco3Giancarlo Ruocco4Rosalba Lepore5Center for Life Nano and Neuro-Science, Istituto Italiano di Tecnologia, Rome, ItalyCenter for Life Nano and Neuro-Science, Istituto Italiano di Tecnologia, Rome, ItalyDepartment of Physics, Sapienza University, Rome, ItalyCenter for Life Nano and Neuro-Science, Istituto Italiano di Tecnologia, Rome, ItalyDepartment of Physics, Sapienza University, Rome, ItalyDepartment of Biomedicine, Basel University Hospital and University of Basel, Basel, SwitzerlandAntibodies have the remarkable ability to recognise their cognate antigens with extraordinary affinity and specificity. Discerning the rules that define antibody-antigen recognition is a fundamental step in the rational design and engineering of functional antibodies with desired properties. In this study we apply the 3D Zernike formalism to the analysis of the surface properties of the antibody complementary determining regions (CDRs). Our results show that shape and electrostatic 3DZD descriptors of the surface of the CDRs are predictive of antigen specificity, with classification accuracy of 81% and area under the receiver operating characteristic curve (AUC) of 0.85. Additionally, while in terms of surface size, solvent accessibility and amino acid composition, antibody epitopes are typically not distinguishable from non-epitope, solvent-exposed regions of the antigen, the 3DZD descriptors detect significantly higher surface complementarity to the paratope, and are able to predict correct paratope-epitope interaction with an AUC = 0.75.https://www.frontiersin.org/articles/10.3389/fmolb.2021.749784/fullsurface complementarityantibody complementarity determining regionsantibody—antigen complexantigen recognitionzernike polynomials |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lorenzo Di Rienzo Edoardo Milanetti Edoardo Milanetti Giancarlo Ruocco Giancarlo Ruocco Rosalba Lepore |
spellingShingle |
Lorenzo Di Rienzo Edoardo Milanetti Edoardo Milanetti Giancarlo Ruocco Giancarlo Ruocco Rosalba Lepore Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces Frontiers in Molecular Biosciences surface complementarity antibody complementarity determining regions antibody—antigen complex antigen recognition zernike polynomials |
author_facet |
Lorenzo Di Rienzo Edoardo Milanetti Edoardo Milanetti Giancarlo Ruocco Giancarlo Ruocco Rosalba Lepore |
author_sort |
Lorenzo Di Rienzo |
title |
Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces |
title_short |
Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces |
title_full |
Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces |
title_fullStr |
Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces |
title_full_unstemmed |
Quantitative Description of Surface Complementarity of Antibody-Antigen Interfaces |
title_sort |
quantitative description of surface complementarity of antibody-antigen interfaces |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2021-09-01 |
description |
Antibodies have the remarkable ability to recognise their cognate antigens with extraordinary affinity and specificity. Discerning the rules that define antibody-antigen recognition is a fundamental step in the rational design and engineering of functional antibodies with desired properties. In this study we apply the 3D Zernike formalism to the analysis of the surface properties of the antibody complementary determining regions (CDRs). Our results show that shape and electrostatic 3DZD descriptors of the surface of the CDRs are predictive of antigen specificity, with classification accuracy of 81% and area under the receiver operating characteristic curve (AUC) of 0.85. Additionally, while in terms of surface size, solvent accessibility and amino acid composition, antibody epitopes are typically not distinguishable from non-epitope, solvent-exposed regions of the antigen, the 3DZD descriptors detect significantly higher surface complementarity to the paratope, and are able to predict correct paratope-epitope interaction with an AUC = 0.75. |
topic |
surface complementarity antibody complementarity determining regions antibody—antigen complex antigen recognition zernike polynomials |
url |
https://www.frontiersin.org/articles/10.3389/fmolb.2021.749784/full |
work_keys_str_mv |
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