# Covalent bond between protein and ligand (cobalamin)

**URL:** <https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996>\
**Category:** User discussions\
**Tags:** pdb2gmx, forcefield, simulation-setup\
**Created:** [October 11, 2022, 1:13pm UTC](https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996 "2022-10-11T13:13:14Z")\
**Posts on this page:** 5\
**Page:** 1

<div class="post-metadata">

**Author:** ![kpounot](https://avatars.discourse-cdn.com/v4/letter/k/b487fb/32.png) [@kpounot](https://gromacs.bioexcel.eu/u/kpounot)\
**Post date:** [October 11, 2022, 1:13pm UTC](https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996/1 "2022-10-11T13:13:14Z")

</div>

Hi everyone,

I would like to run simulation on a protein that is covalently bound to a cobalamin ligand.  
I can generate the starting structure with pdb2gmx by having the protein and the ligand in separate molecules, each described by a different .itp topology file.

But how can I define a covalent bond between an histidine of the protein and the cobalt atom of the cobalamin?  
Does it make sense to define the cobalamin residue as a ‘Protein’ and include it in the same .itp file?

Thanks in advance for your help.

Best,  
Kevin

---

<div class="post-metadata">

**Author:** ![kpounot](https://avatars.discourse-cdn.com/v4/letter/k/b487fb/32.png) [@kpounot](https://gromacs.bioexcel.eu/u/kpounot)\
**Post date:** [October 11, 2022, 2:15pm UTC](https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996/2 "2022-10-11T14:15:20Z")

</div>

I just realized there is a ‘merge’ option in pdb2gmx.

This might actually work, as it generates a single molecule in the ‘topol.top’ file. Also the ‘gmx make\_ndx’ is able to automatically make the distinction between the protein and the cobalamin.

I guess it shall work, but it does make the topology file quite messy, with everything in a same molecule.

Maybe it might be useful to have something to define bonds between different molecules in the future.  
A syntax of the form?:

```auto
[bonds]
molecule_1:atom molecule_2:atom 1

```

Best,  
Kevin

---

<div class="post-metadata">

**Author:** ![ebriand](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/ebriand/32/2314_2.png) [@ebriand](https://gromacs.bioexcel.eu/u/ebriand)\
**Post date:** [October 11, 2022, 3:37pm UTC](https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996/3 "2022-10-11T15:37:32Z")

</div>

For future reference, or if `-merge` does not solve your problem, this is what the `[intermolecular_interactions]` section of the topology can be used for. See [this](https://manual.gromacs.org/documentation/current/reference-manual/topologies/molecule-definition.html) and [this](https://manual.gromacs.org/current/reference-manual/topologies/topology-file-formats.html#tab-topfile1) for details.

---

<div class="post-metadata">

**Author:** ![kpounot](https://avatars.discourse-cdn.com/v4/letter/k/b487fb/32.png) [@kpounot](https://gromacs.bioexcel.eu/u/kpounot)\
**Post date:** [October 11, 2022, 4:28pm UTC](https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996/4 "2022-10-11T16:28:07Z")

</div>

Hi,

Many thanks!  
Don’t know how, I went through the reference but I completely missed this part.

Best,  
Kevin

---

<div class="post-metadata">

**Author:** ![Ravi677](https://avatars.discourse-cdn.com/v4/letter/r/bbe5ce/32.png) [@Ravi677](https://gromacs.bioexcel.eu/u/Ravi677)\
**Post date:** [October 5, 2023, 6:25am UTC](https://gromacs.bioexcel.eu/t/covalent-bond-between-protein-and-ligand-cobalamin/4996/5 "2023-10-05T06:25:43Z")

</div>

Hi kpounot,

Can you please share how you made topology for the cobalamin? I would really appreciate your time and consideration.