Investigation of the solution structure of the human parathyroid hormone fragment (1-34) by sup 1 H NMR spectroscopy, distance geometry, and molecular dynamics calculations

The structure of human parathyroid hormone fragment (1-34) in a solvent mixture of water and trifluoroethanol has been determined by {sup 1}H nuclear magnetic resonance spectroscopy and a combination of distance geometry and molecular dynamic simulations. After complete assignment of the {sup 1}H signals, the nuclear Overhauser enhancement data imply the existence of two {alpha}-helics, comprising residues 3-9 and 17-28, joined by a nonstructured region. The absence of any long-range NOEs and the relative magnitudes of the sequential NOEs and the {sup 3}J(H{sub N}H{sub alpha}) values reflect an inherent flexibility within the entire fragment. The final structures refined by molecular dynamics further support the above results and allow discussion of structural-activity relationships.