GROMACS version: 2024
GROMACS modification: Yes/No
Dear users,
I’d like to know if anyone has some experience simulating dizinc metalloproteins with the CHARMM force field, specifically metallo-beta-lactamases with one of the zincs coordinated by 3 histidines and the other 2 histidines and an aspartate.
I researched the literature but I didn’t find anyone simulating such a system using GROMACS either, usually, these simulations take place either with QM/MM, using bonded parameters in AMBER, or using the cationic dummy method (which can’t be directly transferred to my case anyway because of my geometry).
Approaching the problem with the default parameters for CHARMM36m doesn’t work, as the zinc ions are too close in this pocket, and the localized +2 charge ends up being a poor representation of the system: the ions quickly diffuse away from the pocket as soon as the restraints are lifted after a (very long) equilibration.
I would deeply appreciate some suggestions on how to tackle this problem. The way I see it right now, the most obvious way would be to use amber tools to prepare bonded parameters for Amber and convert the topology to GROMACS afterward.
Thank you very much in advance!
If you don’t need to study the dissociation of the ions, I’d go ahead with ZAFF (there’s an extended version available now).
One could also try to convert the Amber ZAFF files into Gromacs .ff files with this gromologist workflow, I haven’t really tried it before though.
Thank you very much for the advice, Milosz, I’ll give this EZAFF a try!
For anyone who might be interested/troubled by this in the future, I’ve managed to successfully simulate the former dizinc system using the parameters developed by Macchiagodena et al. in her two papers (https://pubs.acs.org/doi/10.1021/acsomega.0c01337?ref=recommended and https://pubs.acs.org/doi/10.1021/acs.jcim.9b00407). I had to implement a hydroxide ion bridging the two zincs, with parameters described as in Marion et al. (https://pubs.acs.org/doi/10.1021/acschembio.6b00847). I found all of this thanks to this excellent and thorough benchmarking by Melse et al. (https://onlinelibrary.wiley.com/doi/full/10.1002/jcc.27052).
Hello, I have recently been conducting protein simulations involving the metal coordinating zinc ion. It is known that my zinc ion forms coordination bonds with four residues in the protein.
I am also confused about how to simulate this metal coordination. I have gone through several forum threads, most of which recommend using bond type 6, meaning adding harmonic potentials to restrain these coordination bonds. However, I have trouble determining the corresponding bond parameters.
I am also utilizing the CHARMM36 force field and have not tried the Amber force field. I have learned about ZAFF, yet it seems to be designed exclusively for the Amber force field.
Could you elaborate on the specific GROMACS configurations you used to simulate this metal coordinating ion? I would highly appreciate any assistance you can offer.
Hi,
As I mentioned in my last post, I gave up on using CHARMM36 and ended up using Amber (I don’t remember which ff exactly, I used the one compatible with the zincs). To do everything in GROMACS, I set up my whole system using CHARMM-GUI, chose the appropriate Amber force field, and selected the GROMACS output format. Then I manually changed the .itp files with the zinc-ion parameters to match those in the papers by Macchiagodena et al., and these worked like a charm for me: the zinc ions were stable across 5 replicas of 1 us each.
I highly recommend checking out her papers and seeing if any of the parameters match the exact geometry you need. In my case, I had zincs with tetrahedral and trigonal bipyramidal coordinations, and both were quite stable.
Cheers!