Conformations of a model cyclic hexapeptide, CYIQNC: (1)H-NMR and molecular dynamics studies.

Solution conformation of the cyclic hexapeptide sequence, [cyclo-S-Cys-Tyr-Ile-Gln-Asn-Cys-S] (CYIQNC) - a disulfide-linked fragment of a neurohypophyseal peptide hormone oxytocin (OT) - has been investigated by high-field one-dimensional (1D) and two-dimensional (2D) NMR spectroscopic methods and compared with the results obtained from computer simulation studies. (1)H-NMR results based on temperature dependence of amide proton chemical shifts and nuclear Overhauser effect indicate that peptide in solution populates different conformations, characterized by two fused β-turns. The segment Ile(3)-Gln(4)-Asn(5)-Cys(6) yields a preferred type-III β-turn at residues 4, 5 (HB, 3HN → 6CO), while the segment Cys(6), Cys(1)-Tyr(2)-Ile(3) exhibits inherently weaker, flexible β-turn either of type I/II'/III/half-turn at residues 1, 2 (HB, 6HN → 3CO).

Combined 1H-NMR and molecular dynamics studies on conformational behavior of a model heptapeptide, GRGDSPC.

Among various strategies, the de novo design and in silico approaches are being used to develop the short peptides, models of modified peptides, and mimetics as clinically useful drugs with improved stability and bioavailability. The resulting models will help to isolate the factors behind the folded structure formation and contribute useful information about de novo peptide design. The combined (1)H-NMR spectroscopic and molecular dynamics methods were used to investigate the conformational behavior of an Arg-Gly-Asp (RGD)-containing peptide, GRGDSPC, the cell-binding heptapeptide of extracellular matrix protein, fibronectin.

Conformational flexibility and loss of structural rigidity for a model hexapeptide, GRGDTP: 1H-NMR and molecular dynamics studies.

The NMR and molecular dynamics methods are used to study the conformations of a hexapeptide, GRGDTP, which has been shown to be accessible to various types of cell-adhesion based cellular behaviors such as cell-to-matrix interactions, cell differentiation, immunogenicity development, gene expression, angiogenesis, metastasis, sex determination and gamete fusion. (1)H-NMR results indicate the existence of weak 5→2 hydrogen bonded β-turn type-III. Molecular simulation studies using a mixed protocol of distance geometry, constrained minimization, restrained molecular dynamics followed by energy minimization resulted additional conformations that include about 64% of population of inverse γ-turn (HB, 3→1) and about 35% population of γ-turn (HB, 4→2).