title: Transitions from alpha to pi helix observed in molecular dynamics simulations of synthetic peptides.
abstract: Molecular dynamics simulations were carried out for three 13-residue peptides of the form AcNH-A-A-E-X-A-E-A-H-A-A-E-K-A-CONH(2) with X = A, F, and W. All three peptides exhibited unexpected dynamical behavior, undergoing a transition from an alpha-helical to a pi-helical structure in the course of 5-ns trajectories in aqueous solution. Analysis of peptide length, accessible surface, interaction energies, hydrogen bonding, and dihedral angles was consistent with alpha --> pi transitions at 2800, 500, and 800 ps for X = A, F and W, respectively. The transitions occurred sequentially and cooperatively, propagating from the C- to the N-terminus for X = A and W and from the center toward both termini for X = F. The time scale of the overall transition ranged from 300 to 500 ps. For all three peptides the backbone structural transition was accompanied by a concerted rearrangement of the charged side chains, including a 3 A increase in the distance between carboxylate groups of Glu-3 and Glu-6. During the transition the peptide backbone hydrogen-bonding patterns were disrupted at the interface between the alpha-helical and nascent pi-helical regions, with peptide groups forming water-bridged hydrogen bonds. The peptide structures exhibited significant fluidity, with individual residues sampling alpha-, pi-, and 3(10)-helical conformations, as well as a "coil" state, without any intramolecular hydrogen bonds. The studied peptides have been designed to form alpha-helices when incorporated in novel hemoprotein model compounds, peptide-sandwiched mesohemes, which consist of two identical peptides covalently attached to an Fe(III) mesoporphyrin [Liu, D., Williamson, D. A., Kennedy, M. L., Williams, T. D., Morton, M. M., and Benson, D. R. (1999) J. Am. Chem. Soc. 121, 11798-11812]. The possibility of adopting pi-helical structures by the constituent peptides may influence the properties of the hemoprotein models.
authors.affiliation: Department of Chemistry, University of Kansas, 2010 Malott Hall, Lawrence, Kansas 66045, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: D R
authors.initials: DR
authors.lastname: Benson
authors.forename: K
authors.initials: K
authors.lastname: Kuczera
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D008652:Mesoporphyrins / Q000737:chemistry; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012997:Solvents; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D008652:Mesoporphyrins; D010455:Peptides; D012997:Solvents; D014867:Water; C031468:mesoporphyrin IX