ComQum (Combined Quantum Mechanical and Molecular Mechanical geometry optimizations) is an approach primarily intended to obtain geometries of active sites in proteins [Ryde, 1996b]. It provides an interface between a QM and a MM program. The philosophy behind it is that no changes should be needed in the codes of these two programs, so that we can always use the best programs available. Therefore ComQum consists of a few small procedures that produce the input files and transfer information between the two programs.
The QM MM approach of ComQum is very similar to the one suggested by Singh and Kollman [Singh and Kollman, 1986] and also used by Hillier and coworkers [Waszkowycz et al., 1991a] [Waszkowycz et al., 1991b] [Waszkowycz et al., 1991c]. It differs from these mainly in the detailed treatment of the junction atoms; the positions of the junction atoms are optimised in the same way as for the other QM atoms, including corrections for the truncation in a way similar to the one used in the ONIOM method [Svensson et al., 1996].
ComQum has successfully been applied in several investigations of the catalytic and structural zinc ions in alcohol dehydrogenase, e.g. to establish the coordination number of zinc during the catalysis, to decide the protonation status of the Cys ligands of zinc, to show that a nearby Glu group intermittently coordinates to zinc, to interpret experimental measurements, and to quantify strain energies of zinc sites when bound to a protein [Ryde, 1995] [Ryde, 1996b] [Ryde, 1996a] [Ryde and Hemmingsen, 1997]. Several of our predictions have later been confirmed by crystallographic studies.