Human Germline Antibody Gene Segments Encode Polyspecific Antibodies
Figure 6
Rosetta multi-state design solutions for non-germline amino acids represent incomplete sampling for VH5-51 complexes.
We evaluated a complete germline reversion of VH5-51 sequence versus the sequences output by multi-state design. (A) Consideration of positions in which the multi-state design algorithm chose a non-germline amino acid for at least 10% of the models where evaluated. The difference in energy of the germline sequence and the multi-state design solution sequence is shown for each position. Bars above 0 represent the multi-state design sequence preferred while bars below the line represent the germline amino acid preference. The horizontal dashed line at 0.7 Rosetta energy units (REU) shows the average energy difference between the germline and mature sequence and is represented as a marker for sequence tolerance. (B) The multiple sequence alignment for each VH5-51 complex is shown and compared with the germline sequence. Sequences highlighted in bold were considered for design. Sequences highlighted in green are positions in which the multi-state design algorithm chose the germline amino acid as the design solution. The numbers in the bottom row are the alignment-numbering scheme of each position and correspond to the position numbers in (A).