A comparison of the structure and dynamics of avian pancreatic polypeptide hormone in solution and in the crystal

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Abstract
A molecular dynamics simulation was carried out with avian pancreatic polypeptide hormone (aPP) as an isolated monomer explicitly including the solvent (MDS). The simulation and the resulting mean structure are compared with the results of a corresponding crystal simulation (MDC) with 4 aPP molecules plus interstitial water in a periodic boundary unit cell and with the X-ray structure (van Gunsteren, Haneef et al., manuscript in preparation). Comparison is based on the time span 5 to 15 ps and considering cartesian coordinates, dihedral angles, H-bond length, and accessible surface area. While in the MDC simulation equilibration is fast and complete, it does occur in MDS for most but not all parts of the molecule; the turn region starts moving away from the X-ray structure after 9 ps. Only minor differences result when dimerforming side chains, e.g. tyrosines 7 and 21, are exposed to solvent. The largest rms fluctuations are encountered in exposed polar side chains of Asp 11, Glu 15, Arg 19, and Arg 33, but also in the hydrophobic core residue Phe 20, the only phenylalanine residue present. The latter undergoes an abrupt reorientation suitable for verification by NMR spectroscopy, which is possibly related to the motion of the turn region. The main-chain dihedral angles of the α-helix are shifted from values generally found in crystal structures towards those of the ideal Pauling helix. There is concomitant H-bond elongation. The effects are most pronounced and consistent in the MDS simulation.