Determination of the backbone conformation of secretin by restrained molecular dynamics on the basis of interproton distance data

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Abstract
The backbone conformation of the 27‐residue polypeptide hormone secretin has been investigated using nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations under conditions where it adopts a fully ordered structure (40% v/v trifluoroethanol). The basis for the restrained molecular dynamics calculations consists of 52 nuclear‐Overhauser‐enhancement‐derived interproton distance restraints involving the NH, CαH and CβH protons. It is shown that convergence to similar extended structures is achieved starting from four different initial structures, namely an α helix, a mixed α/β structure, a β strand and a polyproline helix. The converged structures are made up of short N‐ and C‐terminal strand‐like regions and a central region comprising two irregular helices connected by a ‘half‐turn’.