Fe2+ and Mn2+ force field parameters

GROMACS version: 2019.3
GROMACS modification: Yes/No
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Dear all,

I am trying to do MD simultion on protein in complex with Fe2+ and/or Mn2+. Does anyone know where I can find the force field parameters for these ions and how should I include them in the simulation?

With many thanks!
Best regards

Mn2+ parameters for AMBER: http://research.bmh.manchester.ac.uk/bryce/amber

Mn2+ parameters for CHARMM: dx.doi.org/10.1021/jp309150r

Fe2+ should already be present in both, though is generally designed to only be used in heme (at least for CHARMM), so your mileage may vary for other species.The paper above for CHARMM has new Fe2+ parameters but I have never used them so I cannot vouch for their quality.

Add the relevant parameters to ffnonbonded.itp and if you need pdb2gmx to create a topology with them, also add relevant information to the .rtp and .atp files.

Hello Jalemkul,

Thank you for your reply. I am trying to build the protein-Fe complex with charmm36-mar2019.ff. In the charmm36-mar2019.ff directory, there are the atomtypes.atp, ffnonbonded.itp and merged.rtp files. These files all contains lines for FE. For example, in the ffnonbonded.itp file, there is a line reading:
FE 26 55.847000 0.000 A 0.115816833358 -0.00000
In the atomtypes.atp file, there is a line reading:
FE 55.84700 ; heme iron 56
In the merged.rtp file, there are lines reading:
[ HEME ]
[ atoms ]
FE FE 0.240 0

However, when I use pdb2gmx to build the topology, I get the following error:

Fatal error:
Residue ‘FE’ not found in residue topology database

So Could you further explain how to deal with this situation?
Best regards

There is no standalone residue entry for iron in the force field. There are parameters for the heme Fe2+, and you see it appear in the HEME residue, but there is no FE residue.

What is it that you’re actually dealing with? Free ions? Part of some other cofactor? We need more detail to be able to help.

Hello Jalemkul,

I am just dealing with a Fe-Protein complex, and there is no other co-factor in the complex.
The coordinate for this complex can be found at:
https://drive.google.com/file/d/1jNx8Sfl7v8PY-dGF4mRx5OCKbkr3AduI/view?usp=sharing

Best regards

Follow http://manual.gromacs.org/current/how-to/topology.html#adding-a-new-residue

Be advised that the CHARMM Fe2+ parameters are only developed for heme and have not been validated for His and Asp/Glu interactions like you have in your complex. You should do some validation against QM interaction energies and dimer geometries before trying to just apply the existing parameters. I suspect you will find you need NBFIX terms.

I added the following lines to the merged.rtp file:
[ FE ]
[ atoms ]
FE FE 2.000 0

Now the pdb2gmx has worked through. However, could you also give me some instruction on:
(1) how to validate for Fe2+ interactions with His and Asp/Glu?
(2) how to validate against QM interaction energies?

Best regards

I would recommend you thoroughly read the CHARMM force field papers, many of which describe these aspects in great detail.

Do you mean the paper for the metal ion charmm ff you listed above all Just the Charmm ff paper?
And I wonder what is the most reliable method to calculate the binding free energy between the Fe2+ and the protein, the SMD method or the alchemical method?

Best regards.

Any review of the CHARMM force field will tell you all about how the force field is parametrized, including the proper QM methods.

Decoupling charged species is tricky. My first try would be with SMD, but given the partial covalent nature of the actual interactions of these species with proteins, obtaining something physically realistic may be extremely challenging.