biostudies-literatureKearns FLAustrian Science Fund FWFNational Institutes of HealthNIGMS NIH HHSNIH HHSNational Science FoundationE681https://www.ebi.ac.uk/biostudies/studies/S-EPMC6413162biostudies-literatureUnknown24(4)Indirect (S)QM/MM free energy simulations (FES) are vital to efficiently incorporating sufficient sampling and accurate (QM) energetic evaluations when estimating free energies of practical/experimental interest. Connecting between levels of theory, i.e., calculating Δ A l o w → h i g h , remains to be the most challenging step within an indirect FES protocol. To improve calculations of Δ A l o w → h i g h , we must: (1) compare the performance of all FES methods currently available; and (2) compile and maintain datasets of Δ A l o w → h i g h calculated for a wide-variety of molecules so that future practitioners may replicate or improve upon the current state-of-the-art. Towards these two aims, we introduce a new dataset, "HiPen", which tabulates Δ A g a s M M → 3 o b (the free energy asMolecules (Basel, Switzerland)The Good, the Bad, and the Ugly: "HiPen", a New Dataset for Validating (S)QM/MM Free Energy Simulations.PMC6413162MRI-15315903900101301R01GM129519CHE-1464946P 31024R01 GM129519P31024Boresch SWarrensford LWoodcock HLKearns FLfalseThe Good, the Bad, and the Ugly: "HiPen", a New Dataset for Validating (S)QM/MM Free Energy Simulations.Indirect (S)QM/MM free energy simulations (FES) are vital to efficiently incorporating sufficient sampling and accurate (QM) energetic evaluations when estimating free energies of practical/experimental interest. Connecting between levels of theory, i.e., calculating Δ A l o w → h i g h , remains to be the most challenging step within an indirect FES protocol. To improve calculations of Δ A l o w → h i g h , we must: (1) compare the performance of all FES methods currently available; and (2) compile and maintain datasets of Δ A l o w → h i g h calculated for a wide-variety of molecules so that future practitioners may replicate or improve upon the current state-of-the-art. Towards these two aims, we introduce a new dataset, "HiPen", which tabulates Δ A g a s M M → 3 o b (the free energy as2019-01-01T00:00:00Z2019 Feb2026-04-08T00:16:35.442Z2019-06-06T20:59:12ZS-EPMC64131623076982610.3390/molecules24040681