title: In Silico Generation of Peptides by Replica Exchange Monte Carlo: Docking-Based Optimization of Maltose-Binding-Protein Ligands.
abstract: Short peptides can be designed in silico and synthesized through automated techniques, making them advantageous and versatile protein binders. A number of docking-based algorithms allow for a computational screening of peptides as binders. Here we developed ex-novo peptides targeting the maltose site of the Maltose Binding Protein, the prototypical system for the study of protein ligand recognition. We used a Monte Carlo based protocol, to computationally evolve a set of octapeptides starting from a polialanine sequence. We screened in silico the candidate peptides and characterized their binding abilities by surface plasmon resonance, fluorescence and electrospray ionization mass spectrometry assays. These experiments showed the designed binders to recognize their target with micromolar affinity. We finally discuss the obtained results in the light of further improvement in the ex-novo optimization of peptide based binders.
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Piazzale Kolbe, Udine, Italy; Department of Medical Biotechnology, University of Siena, Policlinico Le Scotte, Viale Bracci, Siena, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, CIRPEB: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi- University of Naples "Federico II", DFM-Scarl, Naples, Italy.
authors.forename: Pasqualina Liana
authors.initials: PL
authors.lastname: Scognamiglio
authors.affiliation: Department of Drug Discovery and Development, Italian Institute of Technology (IIT), Genova, Italy.
authors.forename: Rolando Pablo
authors.initials: RP
authors.lastname: Hong Enriquez
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Santambrogio
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza, Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
authors.affiliation: Department of Pharmacy, CIRPEB: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi- University of Naples "Federico II", DFM-Scarl, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Marasco
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine & Center for Biotechnology Temple University Philadelphia, Pennsylvania, United States of America; Department of Medicine, Surgery & Neuroscience University of Siena, Strada delle Scotte n. 6, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Piazzale Kolbe, Udine, Italy; Department of Biology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Giacinto
authors.initials: G
authors.lastname: Scoles
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Piazzale Kolbe, Udine, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Fortuna
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D005453:Fluorescence; D055767:Immobilized Proteins / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D058619:Maltose-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization; D020349:Surface Plasmon Resonance; D013816:Thermodynamics; D014364:Tryptophan / Q000378:metabolism
chemical_list: D055767:Immobilized Proteins; D008024:Ligands; D058619:Maltose-Binding Proteins; D010455:Peptides; D014364:Tryptophan