PMX tutorial free energy sign

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 (, 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

Hi Hryhory,

yes, I would agree with your interpretation.



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