Calibration of the Quantum/Classical Hamiltonian in Semiempirical QM/MM AM1 and PM3 Methods

We report a theoretical study on the calibration of the semiempirical quantum mechanical/molecular mechanical (QM/MM) Hamiltonian for the interaction of a series of functional groups with a TIP3P water molecule. Both AM1 and PM3 methods are employed to describe the quantum mechanical groups, which include neutral and charged molecules. Following most of the current QM/MM formalisms, the QM/MM Hamiltonian is built up by combining an electrostatic term and a van der Waals 6−12 potential. Owing to the lack of a precise definition of the electrostatic potential in semiempirical methods, various expressions for determining such an electrostatic energy between QM and MM subsystems have been considered. Likewise, the van der Waals parameters have been optimized to reproduce equilibrium geometries and interaction energies for selected complexes computed at the B3LYP level. Comparison is made with other sets of van der Waals parameters reported in the literature. The results reveal the extreme sensitivity of the v...