Successful molecular dynamics simulation of two zinc complexes bridged by a hydroxide in phosphotriesterase using the cationic dummy atom method

I report herein two 2.0 ns (1.0 fs time step) MD simulations of two zinc co mplexes bridged by a hydroxide in phosphotriesterase (PTE) employing the no nbonded method and the cationic dummy atom method that uses virtual atoms t o impose orientational requirement for zinc ligands. The cationic dummy ato m method was able to simulate the four-ligand coordination of the two zinc complexes in PTE. The distance (3.39 +/- 0.07 Angstrom) be. tween two nearb y zinc ions in the time-average structure of PTE derived from the MD simula tion using the cationic dummy atoms matched that in the X-ray structure (3. 31 +/-0.001 Angstrom). Unequivocally, the time-average structure of PTE was able to fit into the experimentally determined difference electron density map of the corresponding X-ray structure. The results demonstrate the prac ticality of the cationic dummy atom method for MD simulations of zinc prote ins bound with multiple zinc ions. In contrast, a 2.0 ns (1.0 fs time step) NM simulation using the nonbonded method revealed a striking difference in the active site between the X-ray structure and the time-average structure that was unable to fit into the density map of PTE. The results suggest th at caution should be used in the MD simulations using the nonbonded method. (C) 2001 Wiley-Liss,Inc.