Instead of randomly selecting substitutions, an alternative strategy can also be employed involving substituting positions of the lead peptide with residues of a similar nature. This approach, referred to as homolog scanning, aims to minimize structural disruption upon side chain substitutions and identify residues that are most important for maintaining function (Fig ). The substitution process is based on a similarity matrix constructed using manually selected amino acid physicochemical properties (Fig ). The following procedure was used to obtain this matrix: