To compare ordered water positions from experiment
with those from molecular dynamics (MD) simulations, a number of MD models of
water structure in crystalline endoglucanase were calculated. The starting MD
model was derived from a joint X-ray and neutron diffraction crystal structure,
enabling the use of experimentally assigned protonation states. Simulations
were performed in the crystalline state, using a periodic 2x2x2 supercell with
explicit solvent. Water X-ray and neutron scattering density maps were computed
from MD trajectories using standard macromolecular crystallography methods. In
one set of simulations, harmonic restraints were applied to bias the protein
structure toward the crystal structure. For these simulations, the recall of
crystallographic waters using strong peaks in the MD water electron density was
very good, and there also was substantial visual agreement between the
boomerang-like wings of the neutron scattering density and the crystalline
water hydrogen positions. An unrestrained simulation also was performed. For
this simulation, the recall of crystallographic waters was much lower. For both
restrained and unrestrained simulations, the strongest water density peaks were
associated with crystallographic waters. The results demonstrate that it is now
possible to recover crystallographic water structure using restrained MD
simulations, but that it is not yet reasonable to expect unrestrained MD
simulations to do the same. Further development and generalization of MD water
models for force field development, macromolecular crystallography, and
medicinal chemistry applications is now warranted. In particular, the
combination of room-temperature crystallography, neutron diffraction, and
crystalline MD simulations promises to substantially advance modeling of
biomolecular solvation.
[UO2(NH3)5]Br2·NH3: synthesis, crystal structure, and speciation in liquid ammonia solution by first-principles molecular dynamics simulations