title: Exploring the sequence space for (tri-)peptide self-assembly to design and discover new hydrogels.
abstract: Peptides that self-assemble into nanostructures are of tremendous interest for biological, medical, photonic and nanotechnological applications. The enormous sequence space that is available from 20 amino acids probably harbours many interesting candidates, but it is currently not possible to predict supramolecular behaviour from sequence alone. Here, we demonstrate computational tools to screen for the aqueous self-assembly propensity in all of the 8,000 possible tripeptides and evaluate these by comparison with known examples. We applied filters to select for candidates that simultaneously optimize the apparently contradicting requirements of aggregation propensity and hydrophilicity, which resulted in a set of design rules for self-assembling sequences. A number of peptides were subsequently synthesized and characterized, including the first reported tripeptides that are able to form a hydrogel at neutral pH. These tools, which enable the peptide sequence space to be searched for supramolecular properties, enable minimalistic peptide nanotechnology to deliver on its promise.
authors.affiliation: 1] WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK [2] SUPA, Department of Physics, University of Strathclyde, 107 Rottenrow East, Glasgow G4 0NG, UK.
authors.forename: Pim W J M
authors.initials: PW
authors.lastname: Frederix
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Scott
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors.forename: Yousef M
authors.initials: YM
authors.lastname: Abul-Haija
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kalafatovic
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors.forename: Charalampos G
authors.initials: CG
authors.lastname: Pappas
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Javid
authors.affiliation: SUPA, Department of Physics, University of Strathclyde, 107 Rottenrow East, Glasgow G4 0NG, UK.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Hunt
authors.affiliation: 1] WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK [2] Advanced Science Research Center and Hunter College, City University of New York, 85 St Nicholas Terrace, New York, New York 10031, USA.
authors.forename: Rein V
authors.initials: RV
authors.lastname: Ulijn
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK.
authors.forename: Tell
authors.initials: T
authors.lastname: Tuttle
mesh_terms: D000595:Amino Acid Sequence; D020100:Hydrogels / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D020100:Hydrogels; D009842:Oligopeptides