Solution conformations of human growth hormone releasing factor: comparison of the restrained molecular dynamics and distance geometry methods for a system without long-range distance data

A series of three-dimensional structures of the 1–29 fragmentof human growth hormone releasing factor in trifluoroethanolhave been determined by molecular dynamics and distance geometrymethods. The resulting structures satisfy information from nuclearOverhauser effect (NOE) distance data and an empirical potentialenergy function. Although the polypeptide was found to havean ordered structure in all simulations, the NOE data were notsufficient for global convergence to a unique three-dimensionalgeometry. Several satisfactory structures have been determined,all of which are extended conformations consisting of a shortß-strand and two -helices (residues 6–13 andresidues 16–29) connected by short segments of less welldefined secondary structure. Because of the lack of NOE dataconnecting the helix segments, their relative orientation isnot uniquely determined.