Two intermolecular disulfide bonds restrict the relative motion between the two involved protein moieties to a hinge movement. The avidity of antibodies is a fundamental immunological function which is influenced by such a hinge region between the two antigen-binding regions. All natural hinges are parallel. Based on simple rules, we designed an antiparallel hinge from scratch. The flapping mode of this de-novo antiparallel hinge peptide reminds one of bird wings. This molecule currently comes closest to the idea of Molecular Bionics.
We characterize the properties of new amino acids by systematically inserting them first in standalone structural motifs and then in synthetic proteins. The properties of bicyclic -turn mimetics, for example, significantly depend on their protein environment. The bicyclic dipeptide Hot=Tap significantly increases the melting temperature of a standalone 14mer -hairpin while considerably decreasing the melting temperature of the protein foldon (3x27 = 81mer) which contains the -hairpin. The rigidifying effect of Hot=Tap at the tip of the -hairpin obviously interferes with the normal modes which contribute to the overall stability of the protein. How do we know? Protein crystals precipitated from the solution which exhibited a measurably higher resolution than all other published foldon cystal structures. The two synthetic variants lead the list of foldon crystals in the protein data bank (pdb).