DENSITY-FUNCTIONAL BASED PARAMETRIZATION OF A VALENCE-BOND METHOD ANDITS APPLICATIONS IN QUANTUM-CLASSICAL MOLECULAR-DYNAMICS SIMULATIONS OF ENZYMATIC-REACTIONS

An approximate valence bond (AVE) method was parametrized at a microsc opic level for proton transfer and hydroxyanion nucleophilic reactions in enzyme catalytic processes. The method was applied to describe hyd rolytic activity of phospholipase A(2). The AVE parametrization is bas ed on density functional and conventional ab initio calculations calib rated with respect to experimental data in the gas phase. The method w as used as a fast generator of the potential energy function in a quan tum-classical molecular dynamics (QCMD) simulations describing atomic motions as well as propagation of the proton wave function in the enzy me active site. The protein environment surrounding the active site an d solvent effects are included in the model via electrostatic interact ions perturbing the original AVE Hamiltonian. (C) 1996 John Wiley & So ns, Inc.