Position-coded multivalent peptide-peptide interactions revealed by tryptophan-scanning mutagenesis.

We demonstrate in this contribution the evidence that significant cooperative binding effect can be identified for the amino acid sites that are determinant to the binding characteristics in peptide-peptide interactions. The analysis of tryptophan-scanning mutagenesis of the 14-mer peptide consisting only of glycine provides a mapping of position-dependent contributions to the binding energy. The pronounced tryptophan-associated peptide-peptide interactions are originated from the indole moieties with the main chains of 14-mer glycines containing N-H and CO moieties. Specifically, with the presence of two tryptophans as determinant amino acids, cooperative binding can be observed, which are dependent on relative positions of the two tryptophans with a "volcano"-like characteristics. An optimal separation of 6-10 amino acids between two adjacent binding sites can be identified to achieve maximal binding interactions.