Dear Dr. Gapsys,
This is a very simple question, just to resolve some possible misinterpretations.
In the 2020 Tutorial (Ligand modification free energy calculations) in the very end there is a phrase “The calculated value is 0.26 kJ/mol, while the ITC value in the publication (Table 1) is 0.4 kJ/mol.” Indeed, when I use the dhdl-output of the Tutorial’s authors (http://pmx.mpibpc.mpg.de/lugano2019_tutorial2/dhdl.tar.gz), I get the alchemical BAR dG for protein of 147.84 kJ/mol and for water of 147.58 kJ/mol and thus calculated ddG of 0.26 kJ/mol. But if I look in Table 1 of the mentioned publication, the binding free energy of lig_1a is -31.3 kJ/mol and of lig_5 is -31.7 kJ/mol. Considering that in the topology the state A corresponded to lig_1a and state B corresponded to lig_5, I would say that the experimental value to compare with is -31.7 - (-31.3) = -0.4 kJ/mol, I mean has a different sign. What do you think?
This is just a more technical question about the sign, everything is still within the chemical accuracy here of course.
Thank you very much in advance!
Hryhory Sinenka, PhD student at Strasbourg University