Shapes of antibody binding sites: qualitative and quantitative analyses based on a geomorphic classification scheme.

The topography of antibody binding sites has been classified into five types that evoke familiar geomorphic features of the Earth. The 229 antibody crystal structures from the Protein Data Bank were analyzed and classified into these classes. Relationships to previous topography classifications by Rees et al., who defined three classes, and Thornton et al., who defined four classes, are identified. An algorithm was developed to identify the antibody binding site class automatically based on the definition and the shape of the binding site. A three-dimensional convex hull was formed around the complementarity determining regions (CDRs) of the antibody. The convex hull was then "trimmed" to fit the binding site by using distance criteria and morphological techniques. Once the program identified the binding site shape, a statistical and distance based analysis was performed to classify automatically the antibody into one of the five geomorphic classes. The five antibody topography classes are as follows: cave (mostly hapten binders), crater (mostly protein and peptide/carbohydrate/nucleic acid binders), canyon, valley, and plain (mostly protein binders). Comparisons of the binding sites of empty and of complexed antibody binding sites gave an indication of how the shape of the binding site is influenced by binding of the antigen.