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

Farhadi, Tayebeh; Hashemian, Seyed MohammadReza

ainst ready compound libraries. The classified results can be examined by linking to appropriate databases. 28, 136 Fragment-based method Replacement with Partial Ligand Alternatives through Computational Enrichment is a fragment-based approach. 137 By using structures of peptide-bound proteins as design anchors, the program can computationally find a non-peptide mimetic for specific determinants of known peptide ligands. 137 Hybrid peptide-driven shape and pharmacophoric method Development and application of strategies for pharmacophore modeling indicate that the medicinal chemistry community has broadly accepted the intuitive nature of the pharmacophore concept. Besides, shape complementarity has been identified as a significant element in the molecular identification between ligands and their targets. 28 In virtual screening efforts, using the pharmacophore-and shape-based techniques distinctly may increase the rate of false-positive results. 128 Therefore, incorporating both pharmacophore-and shape-matching techniques into one program can potentially diminish the rate of false positives. 128 Recently, to discover novel peptidomimetics, a weboriented virtual screening tool named pepMMsMIMIC 138 was developed to pool the conventional pharmacophore matching with shape complementarity. A library of 17 million conformers were extracted from 3.9 million commercially available chemicals and gathered in the MMsINC database. The database was used as a skeleton to develop