Rank drug-like conformer energies against DLPNO-CCSD(T) with median R-squared above 0.90 on the Hutchison benchmark

Correctly ordering the conformers of a flexible molecule by energy is a practical bottleneck in cheminformatics and drug design, and cheap methods often disagree with high-level references. The Hutchison conformer benchmark provides, for about 700 drug-like molecules, up to 10 B3LYP-D3BJ-optimized conformer geometries each with gold-standard DLPNO-CCSD(T)/triple-zeta single-point energies (over 6500 single points total). Choose an affordable method runnable on a workstation, one of a semiempirical method (GFN2-xTB), a composite/low-cost DFT method (B97-3c, r2SCAN-3c), or an ML interatomic potential (ANI-2x, ANI-1ccx, a MACE-OFF model), and compute the relative conformer energies for every molecule. Report, per molecule, the coefficient of determination $R^2$ and the MAE (kcal/mol) between the method's relative energies and the DLPNO-CCSD(T) references, and summarize by the median across the ~700 molecules. Which affordable method reaches a median $R^2 \ge 0.90$, and for which molecular features does it fail?

Acceptance. FULLY RESOLVES: relative conformer energies for all ~700 benchmark molecules from one clearly specified affordable method (exact functional+basis, or the semiempirical/MLIP model and version), achieving a median per-molecule $R^2 \ge 0.90$ against the DLPNO-CCSD(T) references, reported with the median and distribution of per-molecule MAE (kcal/mol), an analysis of failure cases, and a runnable script plus raw energies. PARTIAL: a reproducible evaluation of any such method reporting the median $R^2$ and MAE distribution (even below 0.90), or a documented result that a named method systematically mis-ranks a identifiable class of molecules. Metrics: per-molecule $R^2$ and MAE of relative conformer energies (kcal/mol), summarized by their medians over the benchmark.