Conformation of endothelin in aqueous ethylene glycol determined by1H-NMR and molecular dynamics simulations

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Abstract
The solution conformation of a 21‐residue vasoconstrictor peptide endothelin‐1 (ET‐1) in water‐ethylene glycol has been determined by two‐dimensional 1H‐NMR spectroscopy and constrained molecular dynamics simulations. The N‐terminus (residues 1–4) appears to undergo conformational averaging and no single structure consistent with the NMR constraints could be found for this region. Residues 5–8 form a turn, and residues 9–16 exist in a helical conformation. A flexible ‘hinge’ between residues 8–9 allows various orientations of the turn relative to the helix. Another ‘hinge’ at residue 17 connects the extended C‐terminus to the bicyclic core region (residues 1–15). Residues important for binding and biological activity form a contiguous surface on one side of the helix, with the two disulfides extending from the other side of the helix.