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    A complete, multi-level conformational clustering of antibody complementarity-determining regions

    Nikoloudis, Dimitris and Pitts, Jim E. and Saldanha, José W. (2014) A complete, multi-level conformational clustering of antibody complementarity-determining regions. PeerJ 2 , e456. ISSN 2167-8359.

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    Classification of antibody complementarity-determining region (CDR) conformations is an important step that drives antibody modelling and engineering, prediction from sequence, directed mutagenesis and induced-fit studies, and allows inferences on sequence-to-structure relations. Most of the previous work performed conformational clustering on a reduced set of structures or after application of various structure pre-filtering criteria. In this study, it was judged that a clustering of every available CDR conformation would produce a complete and redundant repertoire, increase the number of sequence examples and allow better decisions on structure validity in the future. In order to cope with the potential increase in data noise, a first-level statistical clustering was performed using structure superposition Root-Mean-Square Deviation (RMSD) as a distance-criterion, coupled with second- and third-level clustering that employed Ramachandran regions for a deeper qualitative classification. The classification of a total of 12,712 CDR conformations is thus presented, along with rich annotation and cluster descriptions, and the results are compared to previous major studies. The present repertoire has procured an improved image of our current CDR Knowledge-Base, with a novel nesting of conformational sensitivity and specificity that can serve as a systematic framework for improved prediction from sequence as well as a number of future studies that would aid in knowledge-based antibody engineering such as humanisation.


    Item Type: Article
    Keyword(s) / Subject(s): Antibody structure, Canonical model, CDR conformation, Dynamic hybrid tree-cut, Humanisation, Clustering, Nested architecture, Redundant repertoire, Prediction
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Depositing User: Jim Pitts
    Date Deposited: 13 Apr 2015 09:40
    Last Modified: 02 Aug 2023 17:15


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