The first, long time scale (16-ns) ligand field molecular dynamics (LFMD) simulations of the oxy form of tyrosinase are reported. The calculations use our existing type 3 copper force field for the peroxido-bridged [Cu(2)O(2)](2+) unit which is here translated from MMFF into the AMBER format together with a new charge scheme. The protein secondary and tertiary structures are not significantly altered by removing the 'caddie' protein, ORF378, which must be bound to tyrosinase before crystals will grow. A comprehensive principal component analysis of the Cartesian coordinates from the final 8 ns shows that the protein backbone is relatively rigid. However, the significant butterfly fold of the [Cu(2)O(2)](2+) moiety observed in the X-ray structure, presumably due to the caddie protein tyrosine at the active site, is absent in the simulations. LFMD gives a clear and persistent distinction between equatorial and axial Cu-N distances, with the latter about 0.2 A longer and remaining syn to each other. However, the two coordination spheres display important differences. LFMD simulations of the symmetric model complex [mu-eta(2):mu(2)-O(2){Cu(Meim)(3)}(2)](2+) (Meim is 5-methyl-1H-imidazole) provide a mechanism for syn-anti interchange of axial ligands which suggests, in combination with the old experimental X-ray data, the new LFMD simulations and traditional coordination chemistry arguments, that His(54) on Cu(A) is 'insipiently axial' and that a combination of a butterfly distortion of the [Cu(2)O(2)](2+) group and a rotation of the Cu(A)(His)(3) moiety converts the vacant, initially axial, binding site on Cu(A) into a much more favourable equatorial site.