Simulations of proteins in water.

Molecular dynamics simulations of hydrated protein crystals have been carried out in only three cases: two simulations of pancreatic trypsin inhibitor (PTI) and one of avian pancreatic polypeptide (aPP). The purpose of such simulations is to evaluate the accuracy and reliability of molecular dynamics simulations of hydrated proteins. A 40-psec simulation on crystalline PTI, involving 4 protein molecules (of 58 amino acids each), 552 water molecules, and 24 Cl- ions is described. Considerations are energetic and structural stability, division of interaction energy among water and protein, and precision of average structure and structural fluctuations compared to X-ray data from a new 0.94-A resolution study of Wlodawer et al. Water and ion dynamics are considered by analysis of diffusional motions and of residence times of water molecules in specific sites.