About: Computational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear Epitope

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Computational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear Epitope
Creator	Baker, David Adachi, Yumiko Bryson, Steve Julien, Jean-Philippe Kalyuzhniy, Oleksandr Schroeter, Alexandria Andrew Ban, Yih-En Azoitei, Mihai Ban, Y.-E Pai, Emil Porter, Justin Schief, William
source	Elsevier; Medline; PMC
abstract	Abstract Computational grafting of functional motifs onto scaffold proteins is a promising way to engineer novel proteins with pre-specified functionalities. Typically, protein grafting involves the transplantation of protein side chains from a functional motif onto structurally homologous regions of scaffold proteins. Using this approach, we previously transplanted the human immunodeficiency virus 2F5 and 4E10 epitopes onto heterologous proteins to design novel “epitope-scaffold” antigens. However, side-chain grafting is limited by the availability of scaffolds with compatible backbone for a given epitope structure and offers no route to modify backbone structure to improve mimicry or binding affinity. To address this, we report here a new and more aggressive computational method—backbone grafting of linear motifs—that transplants the backbone and side chains of linear functional motifs onto scaffold proteins. To test this method, we first used side-chain grafting to design new 2F5 epitope scaffolds with improved biophysical characteristics. We then independently transplanted the 2F5 epitope onto three of the same parent scaffolds using the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone grafting designs showed close agreement with both the computational models and the desired epitope structure. In two cases, backbone grafting scaffolds bound antibody 2F5 with 30- and 9-fold higher affinity than corresponding side-chain grafting designs. These results demonstrate that flexible backbone methods for epitope grafting can significantly improve binding affinities over those achieved by fixed backbone methods alone. Backbone grafting of linear motifs is a general method to transplant functional motifs when backbone remodeling of the target scaffold is necessary.
has issue date	2012-01-06(xsd:dateTime)
bibo:doi	10.1016/j.jmb.2011.10.003
bibo:pmid	22061265
has license	els-covid
sha1sum (hex)	882abd9ead35b19fb10f87136bd8142458d8e3b8
schema:url	https://doi.org/10.1016/j.jmb.2011.10.003
resource representing a document's title	Computational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear Epitope
has PubMed Central identifier	PMC7105911
has PubMed identifier	22061265
schema:publication	Journal of Molecular Biology
resource representing a document's body	covid:882abd9ead35b19fb10f87136bd8142458d8e3b8#body_text
is schema:about of	named entity 'close' named entity 'grafting' named entity 'scaffolds' named entity 'backbone' named entity 'test' named entity 'Crystal structures' named entity 'flexible' named entity 'motifs' named entity 'Epitope' named entity 'Backbone' named entity 'Linear' covid:arg/882abd9ead35b19fb10f87136bd8142458d8e3b8 named entity 'backbone' named entity 'demonstrate' named entity 'cases' named entity 'backbone' named entity 'protein' named entity 'motifs' named entity 'grafting' named entity 'antibody' named entity 'bound' named entity 'scaffold' named entity 'antigens' named entity 'However' named entity 'structurally' named entity 'grafting' named entity 'Computational' named entity 'structurally homologous' named entity 'motif' named entity 'human immunodeficiency virus' named entity 'immunogen' named entity 'Crystal structures' named entity 'scaffold proteins' named entity 'Computational Design' named entity 'epitopes' named entity 'backbone' named entity 'imidazole' named entity 'Protease Inhibitor' named entity 'light chain' named entity 'dimer' named entity 'epitope' named entity 'epitope' named entity 'epitope' named entity 'Novagen' named entity 'epitope' named entity 'epitope' named entity 'motif' named entity 'kanamycin' named entity 'Plasmids' named entity 'motif' named entity 'epitope' named entity 'epitope' named entity 'alanine' named entity 'epitope' named entity 'RMSD' named entity 'Biophysical' named entity 'structural homology' named entity 'antibody' named entity 'epitope' named entity 'high affinity' named entity 'Epitope' named entity 'size-exclusion chromatography' named entity 'epitope' named entity 'protein' named entity 'epitope' named entity '1.1' named entity 'biophysical' named entity 'epitope' named entity 'antibody' named entity 'multimeric'

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