GROMACS modification: No
I would like to calculate a relative binding free energy difference between two
ligands in a protein’s binding site, and I am struggling with the topology there.
The ligands are similar, but have a portion that changes. I want to set up a dual
topology approach. And here I have to make sure that the atoms in
the two parts of the ligand that are different in topology A (lambda=0) and B (lambda=1), do not interact, as they basically overlap. Now, do I have to define
the corresponding exclusions explicitely/manually, or is this perhaps done
automatically by the free energy implementation?
I understand that this question wouid not arise if I used a single topology
approach , but this would not work here because I’d have to turn constraints
into harmonic bonds, and vice versa.
On a related note: when googling for answers to this question I came across
a relatively recent discussion of the developers:
If one of the involved people happens to read this, please let me know whether
the issues discussed there might affect the type of calculation I describe here!
And another one - there is this paper:
Can anybody enlighten me - is this related to the discussion on github
linked above, or is this something entirely different?