Hi,

I tried to parametrize my ligand (69G.sdf) using OpenFF 1.2.1 and the protein (protein.pdb) using AMBER14SB and built the simulation box (and added TIP3P water + ions). I used ParmEd to save *gro and *top files out. However, I found in the *top file (complex.top), the water hydrogen LJ parameters were not correct:

[ atomtypes ]
; name    at.num    mass    charge ptype  sigma      epsilon
H4             1   1.007947  0.00000000  A     0.26495328      0.0656888

After checking the topology file, I found these hydrogen parameters were the same as some hydrogens on the ligand.
For a TIP3P water, the H atoms should have following parameters:

[ atomtypes ]
; name    at.num    mass    charge ptype  sigma      epsilon
H6             1   1.007947  0.00000000  A              1              0

I also tried to build the system without the ligand and I did not have this issue. So I think ParmEd got confused by some hydrogen atoms on the ligand and mistakenly assigned these ligand hydrogen atom type to the water hydrogens when saving the gromacs topology out. Do you have any insights?

I attached my input files and scripts as well.

Here is a list of package versions I used.

openeye-toolkits          2020.1.0                 py37_0    openeye
openforcefield            0.7.1              pyh39e3cac_0    omnia
openforcefields           1.3.0                      py_0    omnia
parmed                    3.4.1            py37hcd2ae1e_0    conda-forge
openmm                    7.5.1            py37h96c4ddf_0    conda-forge

Thanks!

input_scripts.zip