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Proteins. 2018 Apr;86(4):383-392. doi: 10.1002/prot.25453. Epub 2018 Jan 25.

Antibody side chain conformations are position-dependent.

Author information

1
Department of Statistics, University of Oxford, 24-29 St Giles, Oxford, OX1 3LB, United Kingdom.
2
Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center Munich, Nonnenwald 2, Penzberg, 82377, Germany.
3
Chemistry Department, UCB, 208 Bath Road, Slough, SL1 3WE, United Kingdom.

Erratum in

Abstract

Side chain prediction is an integral component of computational antibody design and structure prediction. Current antibody modelling tools use backbone-dependent rotamer libraries with conformations taken from general proteins. Here we present our antibody-specific rotamer library, where rotamers are binned according to their immunogenetics (IMGT) position, rather than their local backbone geometry. We find that for some amino acid types at certain positions, only a restricted number of side chain conformations are ever observed. Using this information, we are able to reduce the breadth of the rotamer sampling space. Based on our rotamer library, we built a side chain predictor, position-dependent antibody rotamer swapper (PEARS). On a blind test set of 95 antibody model structures, PEARS had the highest average χ1 and χ1+2 accuracy (78.7% and 64.8%) compared to three leading backbone-dependent side chain predictors. Our use of IMGT position, rather than backbone ϕ/ψ, meant that PEARS was more robust to errors in the backbone of the model structure. PEARS also achieved the lowest number of side chain-side chain clashes. PEARS is freely available as a web application at http://opig.stats.ox.ac.uk/webapps/pears.

KEYWORDS:

antibodies; antibody design; protein structure prediction; rotamer library; side chain prediction

PMID:
29318667
DOI:
10.1002/prot.25453
[Indexed for MEDLINE]

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