Alignment of V_H and V_L sequences for the antibody (Ab) data sets. Alignments are shown for synthetic Abs (A) and natural Abs (B). Only positions identified to be important for antigen recognition based on a minimum 0.5% contribution in the paratope in synthetic and/or natural Abs are shown. Positions with ≥90% or 70%–90% conservation across the 50 structures chosen per data set are shaded dark or light gray, respectively. Complementarity-determining regions (CDRs) are indicated, according to the existing IMGT definition, by bold lines above the position numbers and numbered according to the IMGT nomenclature (Lefranc et al. 2003). Bold lines below the position numbers indicate alternate CDRs, defined based on the analysis in Figure 2 as continuous stretches of amino acids containing positions that contribute to antigen interaction based on a minimum 0.5% contribution in the paratope in >5% of structures analyzed from the synthetic and/or natural antibody sets. Asterisks indicate residues found outside of CDR definitions that nevertheless contribute to antigen interaction in >5% of structures analyzed.