Human Germline Antibody Gene Segments Encode Polyspecific Antibodies
Figure 4
Modified Colliers de Perles representation of VH gene segments.
The 98 amino acids present in VH 1-69, VH3-23, or VH5-51 are shown in a Collier de Perles two-dimensional representation and numbered according to the IMGT numbering scheme [40]. Hatched circles are missing residues according to the IMGT numbering scheme and are shown to make graphs consistent. Square boxes represent the boundary between framework and CDR loops. The anti-parallel beta-sheets are represented A–F. A dashed line is shown that divides interface residues with residues that were found to be outside of the interface in a majority of the cases. Interface residues are colored with a blue-pink gradient indicating a numerical antigen contact score defined by a change in neighbors between the free and bound complex (see Methods). Non-interface residues are colored with a green-orange gradient according to their degree of burial defined through a neighbor count. Residues that are transparent were not considered for redesign as they were conserved across all complexes considered. (A, B, C) show the germline sequence represented in the immunoglobulin fold with the thickness of each line representing the design bit-score for that position relative to the germline sequence for multi-state design protocols for VH1-69, VH3-23, or VH5-51, respectively. (D, E, F) show the germline sequence represented, but the thickness of the line corresponds to the mature sequence bit-score averaged over each complex for the single-state design protocol for VH1-69, VH3-23, or VH5-51, respectively.