Different Features of anti-Hapten versus anti-Protein Antibodies

Deep binding pocket, enlarged by long CDR L1, CDR H3 in "Open" conformation

Anti-protein antibodies:
Rather flat binding surface, although an aromatic side chain may poke down into a pocket, short CDR L1, CDR H3 in" closed" conformation.

These tendencies apparent from the comparison of natural antibodies could be incorporated and enhanced in the design of synthetic antibody libraries. Furthermore, different positions in the antibody require different randomization strategies - there are better ways to design a library than to splice random peptides to a constant framework.