Comparison of single points vs. DLPNO-CCSD(T)
For conformational evaluation,
For comparison, we considered a wide variety of accessible computational methods:
- Common classical organic force fields: MMFF94,\cite{Halgren_1996,Halgren:1996kn,Halgren:1996ew,Halgren:1996hj,Halgren:1996ux} UFF,\cite{Rappe_1992} GAFF
- Semiempirical wave function: PM7\cite{Stewart_2012}
- Density functional tight binding: GFN1,\cite{Grimme_2017} GFN2\cite{Bannwarth_2018}
- Low-cost density functional approximations: PBEh-3c,\cite{Grimme_2015} B97-3c\cite{Brandenburg_2018}
- Dispersion-corrected density functionals: B3LYP, PBE, ωB97X with dispersion correction (using def2-TZVP basis set)
- Møller-Plesset RI-MP2 (cc-pVTZ basis set)
In the case of the common dispersion-corrected functionals, we also considered both the commonly-used double-zeta def2-SVP and triple-zeta def2-TZVP basis sets to understand the effects of basis set size.
Since some basis sets (i.e., cc-pVTZ) did not support iodine, and some calculations failed to converge, using only the set of molecules in which one or more methods were not run leaves 6511 entries. Of those, 9 molecules (out of 690) had 2 or fewer poses and were also removed, leaving 681 unique molecules and 6500 entries for comparison.
Basis Set Effects
Compare B3LYP with def2-SVP and def2-TZVP
Compare PBE with def2-SVP and def2-TZP
[ table of correlations R^2]
[ table of Spearman correlation \rho ]
Comparison of Timing
A frequent concern for conformer screening is the relative performance. In general, classical molecular force field methods have been preferred since they allow generation of hundreds of conformers per compound in seconds. While traditional high-level ab initio methods are considered a "gold standard" for