Computer-aided design of amino acid-based therapeutics: a review

Farhadi, Tayebeh; Hashemian, Seyed MohammadReza

Sequence-based approach uses the information of conserved regions and analyzes the multiple sequence alignments. This method is directed by the hypothesis that conserved regions are functionally and structurally significant. 13 Computational tools allow the ligand-based peptide design, although they lag behind bioinformatics strategies developed for protein designing. 13 Recently, using a method based on a PAM250 matrix, the relationship between a series of 35 collagen peptides and antiangiogenic activity including proliferation, migration and adhesion was analyzed. 74 The PAM250 matrix captured information of mutation rates among all pairs of amino acids. Based on the results, regions at the C and N termini of the peptides were detected to be significant for an ideal activity and suggested as two distinct binding sites. The approach showed the potential worth of the sequence-based peptide design. 74 In another report, a computational platform called SARvision was developed to support sequence-based design. SARvision signifies an important step for peptide sequence/activity relationship (SAR) analysis. Moreover, it pools the improved visualization abilities with advanced sequence/activity analysis. 75 Compared to small molecules, property-based design methods for peptides are in the early stages of development. In a recent study, the ΔG decomposition per residue and the physicochemical characteristics of amino acids, such as hydrophilicity, hydrophobicity and volume, were used