title: ENPDA: an evolutionary structure-based de novo peptide design algorithm.
abstract: One of the goals of computational chemists is to automate the de novo design of bioactive molecules. Despite significant advances in computational approaches to ligand design and binding energy evaluation, novel procedures for ligand design are required. Evolutionary computation provides a new approach to this design endeavor. We propose an evolutionary tool for de novo peptide design, based on the evaluation of energies for peptide binding to a user-defined protein surface patch. Special emphasis has been placed on the evaluation of the proposed peptides, leading to two different evaluation heuristics. The software developed was successfully tested on the design of ligands for the proteins prolyl oligopeptidase, p53, and DNA gyrase.
authors.affiliation: Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Universitat de Barcelona, Josep Samitier, 1-5, Barcelona, E 08028, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Belda
authors.forename: Sergio
authors.initials: S
authors.lastname: Madurga
authors.forename: Xavier
authors.initials: X
authors.lastname: Llorà
authors.forename: Marc
authors.initials: M
authors.lastname: Martinell
authors.forename: Teresa
authors.initials: T
authors.lastname: Tarragó
authors.forename: Mireia G
authors.initials: MG
authors.lastname: Piqueras
authors.forename: Ernesto
authors.initials: E
authors.lastname: Nicolás
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001499:Bayes Theorem; D001665:Binding Sites / Q000235:genetics; D027081:DNA Gyrase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D019143:Evolution, Molecular; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D011485:Protein Binding; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012984:Software; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D008024:Ligands; D010455:Peptides; D016159:Tumor Suppressor Protein p53; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases; D027081:DNA Gyrase