TY - JOUR UR - https://doi.org/10.7287/peerj.preprints.291v3 DO - 10.7287/peerj.preprints.291v3 TI - A complete, multi-level conformational clustering of antibody complementarity-determining regions AU - Nikoloudis,Dimitris AU - Pitts,Jim E. AU - Saldanha,José W. DA - 2014/03/20 PY - 2014 KW - antibody structure KW - canonical model KW - CDR conformation KW - Dynamic Hybrid tree-cut KW - humanisation KW - clustering KW - nested architecture KW - redundant repertoire KW - prediction AB - 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 12712 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. VL - 2 SP - e291v3 T2 - PeerJ PrePrints JO - PeerJ PrePrints J2 - PeerJ PrePrints SN - 2167-9843 ER -