Computer-implemented design of peptide:receptor signaling complexes for enhanced chemotaxis

The present invention relates to a computer-implemented method for engineering the interaction between a protein and a cognate peptide that are capable of forming a molecular complex, wherein the method comprises (a) preparing in silico a library of test peptides based on the cognate peptide, and the molecular complex of the protein and the cognate peptide; and/or (a') preparing in silico a library of test protein scaffolds based at least on the parts of the protein that participate in forming the molecular complex with the cognate peptide; (b) docking in silico (i) the library of test peptides onto the library of protein scaffolds by modelling peptide-protein molecular complexes, or (ii) the cognate peptide on the library of protein scaffolds, or the library of test peptides onto the protein or the parts of the protein that participate in forming the molecular complex with the cognate peptide by modelling peptide-protein molecular complexes; (c) identifying the test peptides in the library and/or the protein scaffolds in the library for which low interface energy peptide-protein molecular complexes can be modelled, preferably by a combination of flexible peptide docking and/or de novo protein structure building; (d) identifying the interacting amino acids of the test peptides and/or the protein scaffolds in the ensemble of low interface energy modelled peptide-protein molecular complexes of step (c); (e) selecting and substituting in silico one or more of the interacting amino acids of the peptides and/or the protein scaffolds as identified in step (d) based on the ensemble of low interface energy peptide-protein molecular complexes as identified in step (c); and (f) generating in silico based on the peptides with substituted amino acid(s) and/or the protein scaffolds with substituted amino acid(s) of (e) an ensemble of peptides with substituted amino acid(s) and/or the protein scaffolds with substituted amino acid(s) for which the lowest interface energy peptide-protein molecular complexes can be modelled, thereby obtaining engineered peptides and/or proteins being capable of forming a molecular complex with engineered binding characteristics.