In order 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 electron and neutron 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 excellent, and
there also was substantial visual agreement between the boomerang-like wings of
the neutron density and the crystalline water hydrogen positions. An
unrestrained simulation also was performed. For this simulation, the recall of
crystallographic waters was much lower. 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.
Atomic structure and grain shape evolution of nanodiamond during annealing in oxidizing atmosphere from neutron diffraction and MD simulations
