Antibody side chain conformations are position-dependent

Journal article

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 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, PEARS. On a blind test set of 95 antibody model structures, PEARS had the highest average ϰ1 and ϰ1 + 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. This article is protected by copyright. All rights reserved.

Authors: Leem, J; Georges, G; Shi, J; Deane, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Proteins
• Volume: 86
• Issue: 4
• Pages: 383-392
• Publication date: 2018-01-10
• Acceptance date: 2018-01-05
• DOI: 10.1002/prot.25453
• EISSN: 1097-0134
• ISSN: 0887-3585
• Pmid: 29318667
• Language: English
• Keywords: protein structure prediction; antibodies; antibody design; Rotamer Library; aide chain prediction