Predicting antibody complementarity determining region structures without classification.

Antibodies are used extensively in medical and biological research. Their complementarity determining regions (CDRs) define the majority of their antigen binding functionality. CDR structures have been intensively studied and classified (canonical structures). Here we show that CDR structure predict...

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Hauptverfasser: Choi, Y, Deane, C
Format: Journal article
Sprache:English
Veröffentlicht: 2011
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author Choi, Y
Deane, C
author_facet Choi, Y
Deane, C
author_sort Choi, Y
collection OXFORD
description Antibodies are used extensively in medical and biological research. Their complementarity determining regions (CDRs) define the majority of their antigen binding functionality. CDR structures have been intensively studied and classified (canonical structures). Here we show that CDR structure prediction is no different from the standard loop structure prediction problem and predict them without classification. FREAD, a successful database loop prediction technique, is able to produce accurate predictions for all CDR loops (0.81, 0.42, 0.96, 0.98, 0.88 and 2.25 Å RMSD for CDR-L1 to CDR-H3). In order to overcome the relatively poor predictions of CDR-H3, we developed two variants of FREAD, one focused on sequence similarity (FREAD-S) and another which includes contact information (ConFREAD). Both of the methods improve accuracy for CDR-H3 to 1.34 Å and 1.23 Å respectively. The FREAD variants are also tested on homology models and compared to RosettaAntibody (CDR-H3 prediction on models: 1.98 and 2.62 Å for ConFREAD and RosettaAntibody respectively). CDRs are known to change their structural conformations upon binding the antigen. Traditional CDR classifications are based on sequence similarity and do not account for such environment changes. Using a set of antigen-free and antigen-bound structures, we compared our FREAD variants. ConFREAD which includes contact information successfully discriminates the bound and unbound CDR structures and achieves an accuracy of 1.35 Å for bound structures of CDR-H3.
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spelling oxford-uuid:c3684e49-4bf4-4c71-a89d-82fb6ea59e1a2022-03-27T06:16:10ZPredicting antibody complementarity determining region structures without classification.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c3684e49-4bf4-4c71-a89d-82fb6ea59e1aEnglishSymplectic Elements at Oxford2011Choi, YDeane, CAntibodies are used extensively in medical and biological research. Their complementarity determining regions (CDRs) define the majority of their antigen binding functionality. CDR structures have been intensively studied and classified (canonical structures). Here we show that CDR structure prediction is no different from the standard loop structure prediction problem and predict them without classification. FREAD, a successful database loop prediction technique, is able to produce accurate predictions for all CDR loops (0.81, 0.42, 0.96, 0.98, 0.88 and 2.25 Å RMSD for CDR-L1 to CDR-H3). In order to overcome the relatively poor predictions of CDR-H3, we developed two variants of FREAD, one focused on sequence similarity (FREAD-S) and another which includes contact information (ConFREAD). Both of the methods improve accuracy for CDR-H3 to 1.34 Å and 1.23 Å respectively. The FREAD variants are also tested on homology models and compared to RosettaAntibody (CDR-H3 prediction on models: 1.98 and 2.62 Å for ConFREAD and RosettaAntibody respectively). CDRs are known to change their structural conformations upon binding the antigen. Traditional CDR classifications are based on sequence similarity and do not account for such environment changes. Using a set of antigen-free and antigen-bound structures, we compared our FREAD variants. ConFREAD which includes contact information successfully discriminates the bound and unbound CDR structures and achieves an accuracy of 1.35 Å for bound structures of CDR-H3.
spellingShingle Choi, Y
Deane, C
Predicting antibody complementarity determining region structures without classification.
title Predicting antibody complementarity determining region structures without classification.
title_full Predicting antibody complementarity determining region structures without classification.
title_fullStr Predicting antibody complementarity determining region structures without classification.
title_full_unstemmed Predicting antibody complementarity determining region structures without classification.
title_short Predicting antibody complementarity determining region structures without classification.
title_sort predicting antibody complementarity determining region structures without classification
work_keys_str_mv AT choiy predictingantibodycomplementaritydeterminingregionstructureswithoutclassification
AT deanec predictingantibodycomplementaritydeterminingregionstructureswithoutclassification