DYNAMIC FORCE-FIELD MODELS - MOLECULAR-DYNAMICS SIMULATIONS OF HUMAN CARBONIC-ANHYDRASE-II USING A QUANTUM-MECHANICAL MOLECULAR MECHANICAL COUPLED POTENTIAL

We report extended molecular dynamics simulations of the enzyme human carbonic anhydrase II using a quantum mechanical/molecular mechanical coupled potential. This method allows us to treat the key active site residues of this metalloenzyme using semiempirical quantum mechanics, while directly incorporating the effects of the surrounding enzymatic environment into the electronic structure calculations. Furthermore, this approach provides complete geometric freedom within the zinc coordination sphere and also enables examination of the relative importance of geometric and environmental effects upon atomic charge.