  We have carried out a large scale computational investigation to assess the
utility of common small-molecule force fields for computational screening of
low energy conformers of typical organic molecules. Using statistical analyses
on the energies and relative rankings of up to 250 diverse conformers of 700
different molecular structures, we find that energies from widely-used
classical force fields (MMFF94, UFF, and GAFF) show unconditionally poor energy
and rank correlation with semiempirical (PM7) and Kohn-Sham density functional
theory (DFT) energies calculated at PM7 and DFT optimized geometries. In
contrast, semiempirical PM7 calculations show significantly better correlation
with DFT calculations and generally better geometries. With these results, we
make recommendations to more reliably carry out conformer screening.
