Only molecular mechanics methods are fast enough to allow for a virtual screening of large sets of molecules.
Chemical reactions seem to require theoretical methods that account for the redistribution of electrons as is essential to the bond breaking and bond forming steps. So, with metal atoms in the catalysts today only ab initio methods can be applied.
Nevertheless, with the geometry of the transition state structures and thus the electronic factors known (e.g. from ab initio studies) the differences in the relative stability of the transition states for different molecules may well be determined by the availability of low energy strain-free non-repulsive conformations. This is for a long time inherent to the simple models for selectivity.
The exact arrangement of the reacting centers in the transition state can well be reproduced by an appropriately parametrized force field. The then important relative stabilities of concurrent transition states can well be assessed and thus the selectivity predicted.
We have applied this approach successfully to a metal catalyzed addition reaction within a fully automated catalyst structure generation and substrate validation procedure that allows for a virtual screening of new potential catalysts.