title: Characterisation of the solution conformation of a cyclic RGD peptide analogue by NMR spectroscopy allied with a genetic algorithm approach and constrained molecular dynamics.
abstract: The solution conformation of a cyclic RGD peptide analogue, cyclo-(S,S)-2-mercaptobenzoate-arginine-glycine-aspartate-2-mer captoanilide, has been determined via two independent approaches for the searching of conformational space and identification of conformations consistent with NMR and CD spectroscopic data: (i) the use of a binary genetic algorithm and (ii) a molecular dynamics simulation. Inter-proton distances were obtained via analysis of cross-peak volumes from a two-dimensional ROESY NMR spectroscopy experiment at 600 MHz and were used as constraints for the computational calculations. The mercaptoanilide amide proton resonance chemical shift had a very small temperature coefficient, indicating that this proton was hydrogen-bonded. Circular dichroism data showed that, in solution, the torsion angle about the disulfide bond was negative, consistent with one of the distinct conformations around this bond in the 200 ps molecular dynamics simulation. The backbone conformations of the structures resulting from the two different approaches were very similar.
authors.affiliation: Department of Physical Sciences, Wellcome Research Laboratories, Beckenham, Kent, UK.
authors.forename: P N
authors.initials: PN
authors.lastname: Sanderson
authors.forename: R C
authors.initials: RC
authors.lastname: Glen
authors.forename: A W
authors.initials: AW
authors.lastname: Payne
authors.forename: B D
authors.initials: BD
authors.lastname: Hudson
authors.forename: C
authors.initials: C
authors.lastname: Heide
authors.forename: G E
authors.initials: GE
authors.lastname: Tranter
authors.forename: P M
authors.initials: PM
authors.lastname: Doyle
authors.forename: C J
authors.initials: CJ
authors.lastname: Harris
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000577:Amides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D012996:Solutions; C089691:cyclo-(S,S)-2-mercaptobenzoate-arginyl-glycyl-aspartyl-2-mercaptoanilide; C047981:arginyl-glycyl-aspartic acid; D004121:Dimethyl Sulfoxide