Canonical Classes

The new Canonicals page points the user to canonical (typical) residues responsible for a predicted CDR conformation as well as accessibilities and key interactions in an antibody.

Directly below the antibody sequence are rows of information that describe:

• Residue Numbering
• Framework and CDR regions
• Structural determinants of each CDR based on information from a particular type of analysis. In abYsis there is a choice of three Canonical Schemes for CDR prediction; auto, abm and strict. (See separate section for details on these).
  For the chosen Canonical Scheme, where a residue position is predicted to be important for a CDR conformation a circle is shown. This will be green if the residue is consistent with requirements, if red it is not.
• Secondary Structure; shown as blue arrows.
• Accessibility (Access); divided into four broad classifications; Fully Buried (F) , Buried (B), Intermediate (I) and Exposed (E).
• Residues that often play a role in VH/VL structure Interactions and Determinants are similarly highlighted.

Finally information from a review article by Kuramochi et al. ^* is displayed in two further rows Core (Kur); definitions of Upper and Lower core from Table 1 of their publication VH/VL (Kur) residue positions associated with to the VH/VL interface.

^*Kuramochi, Igawa, Tsunoda and Hattori: (2014) Human Monoclonal Antibodies: Methods and Protocols, Methods in Molecular Biology, vol. 1060

Auto Method

The default option. Based on templates derived automatically from available crystal structures; see Martin and Thornton, J. Mol. Biol. 263(1996),800-815). Canonical class identifiers comprise Chothia class, a cluster number for loop length and a letter to describe the individual cluster. Where there is no equivalent Chothia class, '?' appears (e.g. for CDR-H1, there are classes ?/10C and ?/10D).

AbM Method

AbM key residues are based on Chothia templates (Whitelegg N & Rees AR, Protein Eng. 13(2000),819-24 and Methods Mol. Biol. 248(2004),51-91). The classes are expanded from the Chothia definitions: some additional allowed residues have been specified together with some additional required residues and extra classes. Classes with a * in the name are not defined by Chothia. Modfications and references are detailed for each class.

Strict Method

Strict application of templates derived from an aggregation of papers by Chothia et al.