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

Farhadi, Tayebeh; Hashemian, Seyed MohammadReza

e recognition by the SH3 domain, a number of molecular modeling experiments such as homology modeling, molecular docking and mechanism dynamics were used. 119 Peptide array strategies confirmed that some peptide candidates may be potent binders of the Abl SH3 domain. 120 Very recently, an approach including quantum mechanics/molecular mechanics, semiempirical Poisson-Boltzmann/surface area and empirical conformational free energy analysis was developed to quantitatively illustrate the energetic contributions involved in the affinity losing of PDZ domain and OppA protein to their peptide ligands. 121, 122 De novo peptide design Recently, in order to de novo target-based peptide design, two remarkable methodologies including the VitAL method and an approach developed by Bhattacherjee and Wallin were introduced. The VitAL method pools verterbi algorithm with AutoDock to design peptides for the binding sites of a target. 123 The "Bhattacherjee and Wallin" approach explores both peptide sequence and conformational space around a protein target at the same time. 124 This approach was tested on three dissimilar peptide-protein domains to assess its ability. 13 A brief list of the existing computational resources employed in peptide design is presented in Table 2 .