Density functional based parametrization of a valence bond method and its applications in quantum-classical molecular dynamics simulations of enzymatic reactions

An approximate valence bond (AVB) method was parametrized at a microscopic level for proton transfer and hydroxyanion nucleophilic reactions in enzyme catalytic processes. The method was applied to describe hydrolytic activity of phospholipase A₂. The AVB parametrization is based on density functional and conventional ab initio calculations calibrated with respect to experimental data in the gas phase. The method was used as a fast generator of the potential energy function in a quantum-classical molecular dynamics (QCMD) simulations describing atomic motions as well as propagation of the proton wave function in the enzyme active site. The protein environment surrounding the active site and solvent effects are included in the model via electrostatic interactions perturbing the original AVB Hamiltonian. © 1996 John Wiley & Sons, Inc.