Principal Investigator

J E Gready Computational Molecular Biology, JCSMR, ANU

Project Title

Evaluation of the Potential of MOZYME for the Study of Enzyme Reaction Mechanisms

Brief Description for General Publications

Developments in applications software, coupled with increased HPC power which make very large calculations feasible, have created the expectation of a new era of large-scale biomolecular computation. One such development is MOZYME, a unique program module within the computational chemistry program MOPAC, which allows calculations to be undertaken at an approximate quantum mechanical (semiempirical QM) level on molecules with thousands of atoms. MOZYME is one of a few so-called linear-scaling (LC) QM methods, introduced recently, which achieve this capability by overcoming the bottle-neck of standard QM methods — the N**3 (or higher; N = no of orbitals) computational dependence. MOZYME LC is based on a localised molecular orbital method developed by J.J.P. Stewart, the originator of MOPAC. For conventional QM methods, the N**3 dependence limits calculations to 50-100 atoms (ab initio QM) or a few hundred atoms (semiempirical QM, as in MOPAC and MOZYME). This new capability to compute molecular properties and energies for such large molecules at an all-QM level, provides the opportunity to test the usefulness of MOZYME in real applications. We started with a problem for which MOZYME had been proposed, that is, studying enzyme reaction mechanisms, and compared its performance with another type of new method, hybrid quantum mechanical/mechanical methods (QM/MM) which overcomes the QM computational bottleneck in a completely different way. We also employed MOZYME to study protein properties in other contexts where an all-QM calculation would seem advantageous.