ENPDA: an evolutionary structure-based de novo peptide design algorithm.
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.
Belda
Ignasi
I
Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Universitat de Barcelona, Josep Samitier, 1-5, Barcelona, E 08028, Spain.
Madurga
Sergio
S
Llorà
Xavier
X
Martinell
Marc
M
Tarragó
Teresa
T
Piqueras
Mireia G
MG
Nicolás
Ernesto
E
Giralt
Ernest
E
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
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