Nuclear magnetic resonance studies and molecular dynamics simulations of the solution conformation of a 'designed', alpha-helical peptide.
The complete three-dimensional structure in methanol of an amphipathic alpha-helical peptide, that has been designed by taking into account the three-dimensional structures of small haemolytic peptides, secondary structure prediction algorithms and the well documented literature on alpha-helix stabilizing factors, has been elucidated by two-dimensional NMR spectroscopy. Initially various two-dimensional spectra (COSY, TOCSY, and NOESY) allowed the complete sequence specific assignment of all signals in the 1H spectrum. Consequently trial structures were generated which were then subjected to molecular dynamics simulations using 121 NOE-derived distances and 25 vicinal coupling constant values as structural restraints to give a final set of calculated structures. These structures are in complete agreement with the results of a circular dichroism study and reveal that the peptide adopted a highly ordered alpha-helical conformation. Details of the structure which throw light on future peptide/protein design are discussed.
Klaus
W
W
Gesellschaft für Biotechnologische Forschung (GBF), Abt. Molekulare, Strukturforschung, Braunschweig, Germany.
Moser
R
R
D000595:Amino Acid Sequence; D006460:Hemolysin Proteins / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011522:Protons; D013501:Surface-Active Agents / Q000737:chemistry*
D006460:Hemolysin Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011522:Protons; D013501:Surface-Active Agents; C077195:helical erythrocyte lysing peptide; D000432:Methanol