Computational Chemistry and Molecular Modeling
Atomic, Molecular and Optical Physics
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The synthetic polytetrapeptide using the repeating sequence VPGG found in the fibrous protein, elastin, exhibits a reversible inverse temperature transition, i.e., the molecular order increases on raising the temperature of the polypeptide in aqueous solutions. The matrices formed from the coacervate by γ-irradiation-induced cross-linking exhibit an elastic modulus and temperature dependence of elastomeric force with similarity to that of fibrous elastin. As demonstrated on poly(VPGVG), which forms a β-spiral structure with recurring Type II β-turns, the molecular structure of the elastin-based polypeptides is fundamental to an understanding of the mechanism of elasticity.It was found previously that the repeating unit VPGG in the polytetrapeptide forms a Type II β-turn with a hydrogen bond between Val1 C=O and Gly4 NH. This secondary structural feature is confirmed in this report by 2D NMR data as indicated by specific NOE cross-peaks, particularly, dNN(3,4), dαN(2,3), dαN(2,4), and dγN(1,4). The same secondary structural feature is found in the 2D NMR data for its analog polypeptide, poly(IPGG).The NMR data provide conclusive evidence for the Type II β-turn secondary structure. Molecular mechanics computations were performed to develop a more detailed tertiary structure for the polytetrapeptides. The ECEPP/2 potential field and build-up strategy were employed in mapping conformational space of VPGG and its high polymer. In addition, helical structures are sought using the Go-Scheraga condition, on the assumption that the repeated sequence would preferentially adopt a helical or nearhelical conformation on optimization of intramolecular hydrophobic contacts. A number of structures with helically recurring β-turns was obtained and can be used as starting structures in future studies that are to include hydration. The structures were also evaluated in terms of potential energy using the CHARMm force field.
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