In Search of the Best Low-Cost Methods for Efficient Screening of Conformers

Locating the lowest energy conformer is crucial for the
accurate
computation of equilibrium properties of molecular systems. This paper
examines the performance of efficient low-cost methods in terms of
the alignment and relative energies of their energy minima against
the benchmark revDSD-PBEP86-D4/def2-TZVPP//MP2/cc-pVTZ potential energy
surface. The low-cost methods considered include GFN-FF, GFN2-xTB,
DFTB3, HF-3c, B97-3c, PBEh-3c, and r2SCAN-3c composite
methods against a diverse test set of 20 compounds including alkanes,
perfluoroalkyl molecules, peptides, open-shell radicals, and Zn(II)
complexes of varying sizes. The “3c” composite methods
are generally more accurate, but are at least 2–3 orders of
magnitude more expensive than tight-binding methods which have energy
minima that align well with the benchmark potential energy surface.
The findings of this paper were further exploited to introduce a simple
strategy involving Grimme’s CENSO energy-sorting algorithm
that resulted in up to an order of magnitude reduction in computational
time for locating the lowest energy conformer on the revDSD-PBEP86-D4/def2-TZVPP//MP2/cc-pVTZ
surface.