title: Molecular dynamics conformational search of six cyclic peptides used in the template assembled synthetic protein approach for protein de novo design.
abstract: Six cyclic peptides, designed to act as topological templates in the TASP (template assembled synthetic protein) approach in protein de novo design, were investigated employing a 100-ps, 900-K molecular dynamics conformational search. The peptides are composed of two Lys-X-Lys (X = Gly, Ala) tripeptides connected at its N- and C-terminal end by a Pro-Gly motif and a cystine bridge (I), two Pro-Gly units (II), naphthalene derivatives (III), and tetrahydronaphthalene derivatives of different stereochemistry (IV-VI). The molecular dynamics conformational search established that template I had beta-sheet like geometry. Templates II-VI showed different preferential geometries, among them, e.g., distinct preferences for type V turns in Pro-Gly containing peptides and close spatial arrangement of hydrophobic naphthalene moieties. The orientation of the lysine side chains within preferential geometries of the individual templates is analyzed and a tentative evaluation for their potential to stabilize TASP molecules of 4-helix bundle topology is given.
authors.affiliation: Université de Lausanne, Section de chimie, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Floegel
authors.forename: M
authors.initials: M
authors.lastname: Mutter
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic