De Novo design of protein secondary and super-secondary structural elements : Insights from the crystal structures of a,B-dehydrophenylalanine containing oligopeptides- a novel weak-interaction based design strategy

Abstract

The surface complementarity (charge, structural, etc.) plays a vital role in molecular recognition and association.

It appears that the modes of interaction between aliphatic–aliphatic, aliphatic–aromatic, and aromatic–aromatic residues are different. If so, these factors govern the association of molecules containing both aromatic and aliphatic moieties, possibly producing aromatic–aliphatic patterning in their association.

The molecular recognition and association observed in peptides VI and VIII support the view that weak hydrogen bonds do not play a passive role nor arise merely from geometrical constraints imposed by other contacts. Growing observations and the importance of weak interactions in various fields suggest their recruitment in future work on de novo design.

The mode of docking between two adjacent peptide helices, assisted by weak hydrogen bonds, observed in this study (peptide VII), is to our knowledge the first of its kind. It is therefore tempting to suggest that connecting the two interacting antiparallel ambidextrous helices with a linker, along with slight modification in the sequence to maintain a left-handed 3???helix at one end and a right?handed 3???helix at the other-without disturbing the aromatic residues in the helix-helix interface-might result in the design of a helix–turn–helix supersecondary structural motif.