A Quantum-Classical Molecular Dynamics model (QCMD), applying explicit integration of the time-dependent Schroedinger equation (QD) and Newtonian equations of motion (MD), is presented. The model is capable of describing quantum dynamical processes in complex biomolecular systems. It has been applied in simulations of a multi-step catalytic process carried out by phospholipase A2 in its active site. The process includes quantum-dynamical proton transfer from a water molecule to histidine localized in the active site, followed by a nucleophilic attack of the resulting OH- group on a carbonyl carbon atom of a phospholipid substrate, leading to cleavage of an adjacent ester bond. The process has been simulated using a parallel version of the QCMD code. The potential energy function for the active site is computed using an Approximate Valence Bond (AVB) method. The dynamics of the key proton is described either by QD or classical MD. The coupling between the quantum proton and the classical atoms is accomplished via Hellmann-Feynman forces, as well as the time-dependence of the potential energy function in the Schroedinger equation (QCMD/AVB model).
Analysis of the simulation results using an Advanced Visualization System (AVS) revealed a correlated rather than a stepwise picture of the enzymatic process. It is shown that an sp2 -> sp3 configurational change at the substrate carbonyl carbon is mostly responsible for triggering the activation process.