A molecular mechanical analysis of the active site of urease with a special emphasis on determining the binding conformations available to oxygen-bound urea.

In order to model the active site of urease which contains two nickel ions with differing coordination geometries new parameters were derived for the AMBER* force field. These parameters were obtained by structure based optimization and use a single set of parameters with points on a sphere approach to model nickel(II) high-spin in all its coordination geometries. The force field was successfully used to model the active site of urease and to predict that a bridging water between the two nickel ions in urease was missing from the solid state structure of urease. A thorough conformational search was undertaken to find the conformations available to urea within urease. All the low energy conformations found were used to determine a consensus urea binding model.