Disclaimer: These are preliminary results and may contain errors
This work is licensed under a Creative Commons Attribution 4.0
In a previous post I showed that minimising RDKit-generated conformers generated with MMFF led to slightly worse PM3/COSMO pKa predictions. One reason might be that the MMFF minimisation is done in the gas phase. Anders Christensen reminded me that TINKER can do MMFF/GBSA minimisations so I used TINKER so minimise 20 and 50 RDKit-generated conformers in used these as initial guesses for the PM3/COSMO energy minimisations (20mmtk and 50mmtk
As you can see there is relatively little difference in the overall performance of Xmm and Xmmtk. The error distribution is a bit tighter for the tk variants and 50mmtk does better at finding structures closer to the "global" minimum, but 50nomm is still the best choice for avoiding >1 pKa errors.
So, either GBSA is not a good substitute for COSMO or MMFF is not a good substitute for PM3. In light of this recent paper my money is on the latter. So I'll go with 50nomm for now.
This work is licensed under a Creative Commons Attribution 4.0
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