Core structural paratope of the analyzed synthetic antibodies (Abs). The core structural paratope of the analyzed synthetic Abs was defined as positions that are present in ≥60% of the selected structures and contribute to antigen recognition in ≥20% of the structures. The same positions in natural Abs are shown for comparison. (A) For each position in the core structural paratope of synthetic Abs, the amino acid distributions are shown for synthetic Abs (top) and natural Abs (bottom). Amino acids that are present at ≥10% frequency are shown separately (colored bars), whereas amino acids present at <10% frequency are grouped together as “other” (gray bars). The length of each bar is proportional to the frequency, and the total length of the bars at each position is equal to 100%. (B) The core structural paratope of synthetic Abs mapped onto the structure of the trastuzumab antigen-binding fragment (Fab) (Protein Data Bank entry 1N8Z). The size of each sphere is proportional to the frequency at which residues at that position contribute to antigen recognition in synthetic Abs (left) and natural Abs (right).