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  • Title: Dynamics of a type VI reverse turn in a linear peptide in aqueous solution.
    Author: Demchuk E, Bashford D, Case DA.
    Journal: Fold Des; 1997; 2(1):35-46. PubMed ID: 9080197.
    Abstract:
    BACKGROUND: Peptide sequences with aromatic groups flanking a cis-proline residue are known to have a high propensity for adopting compact structures in which the aromatic sidechains pack against the proline ring. In particular, the sequence Ser-Tyr-Pro-Phe-Asp-Val (and variants of this) is known by NMR to form a high proportion of type VI turns in aqueous solution. We set out to explore the energetic and dynamic features of such sequences using molecular dynamics simulation techniques. RESULTS: The conformation properties of the linear pentapeptide NH3(+)-Ala-Tyr-cisPro-Tyr-Asp-NMA (cis-AYPYD) have been explored in three solvated molecular dynamics simulations. The first began from an NMR-derived model structure containing a type VIa turn and close-stacking interactions between the tyrosine and proline sidechains. During 20 ns of simulation, the peptide made transitions between type VIa and VIb turns, but did not 'unfold' to more extended conformers, consistent with the unusual stability for folded forms observed by NMR for this sequence. Distances monitored by nuclear Overhauser peaks and sidechain rotamer populations in the trajectory are in good agreement with NMR data. Two additional 5 ns trajectories were begun from more extended conformers. The first folded into a conformer much like the NMR-derived structure within 3 ns and remained folded for the remainder of the trajectory. The second was begun from a structure in which the sidechain orientations were deliberately misfolded relative to that required for turn formation; this structure did not make a transition to a turn-like state. CONCLUSIONS: The kinetic stability of folded forms of AYPYD, along with the observation of spontaneous folding from an extended conformation, indicates that the special stability seen experimentally is reflected in computer simulations. The results provide new information about the stabilization of secondary structure in short peptides, particularly by aromatic-proline interactions, and offer a description of pathways of interconversion of type VIa and VIb turns.
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