# CHARMM parameterization destroys ligand structure

**URL:** <https://gromacs.bioexcel.eu/t/charmm-parameterization-destroys-ligand-structure/8372>\
**Category:** User discussions\
**Tags:** forcefield\
**Created:** [February 19, 2024, 1:44pm UTC](https://gromacs.bioexcel.eu/t/charmm-parameterization-destroys-ligand-structure/8372 "2024-02-19T13:44:01Z")\
**Posts on this page:** 1\
**Page:** 1

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**Author:** ![entropybit](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/entropybit/32/4603_2.png) [@entropybit](https://gromacs.bioexcel.eu/u/entropybit)\
**Post date:** [February 19, 2024, 1:44pm UTC](https://gromacs.bioexcel.eu/t/charmm-parameterization-destroys-ligand-structure/8372/1 "2024-02-19T13:44:01Z")

</div>

GROMACS version: 2023.3  
GROMACS modification: No

Hi,

I have successfully parametrized ligands for a Protein-Ligand MD simulation with CGenFF before. However, I noticed that with a specific ligand the cgenff\_charmm2gmx script produces a LIGANDNAME\_ini.pdb file in which the ligands structure is completely lost in comparison with the input mol2 file.  
To show what I mean I have uploaded a pictures of the structure after parametrization. As visible this is not a normal small molecule structure but rather a mess of atoms and bonds.

I can also give the mol2 file of the ligand (but apparently its not allowed to upload this here).

The to be parametrized ligand was one that came out of a ML generative model and for which I then generated a 3D structure in rdkit. Is there maybe some kind of bias in the cgenff\_chamm2gmx script so that “unrealistic” molecules do not get parametrized properly ? In this case I think some kind of warning or failing behavior would be expected.  
In any case I hope someone can help with this.

 ![out](https://europe1.discourse-cdn.com/flex017/uploads/bioexcel1/original/2X/1/10f0d2136828fe92c3de256f3d2a822e791b5352.png)