  A new approach is presented to improve the performance of semiempirical
quantum mechanical (SQM) methods in the description of noncovalent
interactions. To show the strategy, the PM6 Hamiltonian was selected, although,
in general, the procedure can be applied to other semiempirical Hamiltonians
and to different methodologies. In this way, analytical corrections to PM6 were
derived from fits to CCSD(T) - PM6 interaction energy differences. A set of
small molecules was selected as representative of the common functional groups,
and intermolecular potential energy curves were evaluated for the most relevant
orientations of interacting molecular pairs. The resulting method, called
PM6-FGC (from Functional Group Corrections), significantly improves the
performance of PM6 and previous corrected SQM methods, and shows the importance
of including a sufficient number of orientations of the interacting molecules
in the reference data set in order to obtain well-balanced descriptions.
