Amber FF parameters for metal binding centres

GROMACS version: 2021.2
GROMACS modification: No

Dear all,

I would be very grateful for an update on the latest, greatest and perhaps easiest third party tool for the parameterization of the Amber FF (packaged with Gromacs) for the inclusion of zinc and copper in protein ligand-binding sites.

Some years back, I calculated my own set of partial charges, bond equilibrium values and force constants, for similar protein ligand-binding sites. However, at the time the software required Gaussian software calculations and the process of updating the FF was very laborious and awfully time-consuming. Today, I neither have a Gaussian license nor the same amount of free time. Essentially, I am hoping to find software (or a pipeline of software) that will calculate the following for three sets of metal-sidechain groups:

-bond, angle, dihedral and improper dihedral force constants
-topology equilibrium constants i.e., bond and angle values
-partial charges

Any suggestions are kindly appreciated.

Thanks, Anthony.


I ran many simulations with Zinc added, based on the work for Amber by Peters et al.

I modified the force field for 2 His, 2 Cys Zn centres.

I also modified the force field for 4 Cys Zn centres.

I’m afraid that doesn’t help you with Copper, but if it is useful, please let me know.

On the page describing ZAFF (above), there is a link to MCPB and that might help with copper.


Thanks for the information. I have two zinc coordination sites (and two copper), one with 5 and the other with 6 side chains. Sadly that means much of the information on that page won’t work. However, I’ll look into MCPB.

Personally, I was hoping to find something a lot more ‘light weight’ than going down the Amber toolset route. It’s been quite a few years since I last looked at it. But I guess, needs must.

Thanks again


In addition to aforementioned bonded type models (e.g. ZAFF), other options that may work are the cation dummy atom models or there are also some fairly recent non-bonded models that use 12-6-4 potentials. For the former you can likely use GROMACS (I’ve done so with a cation dummy atom zinc model previously), while for the latter I believe you will need to use another bit of software such as AMBER. Whatever way you go, to get these types of systems to work properly isn’t trivial and will require a fair bit of effort. Aside from these, the other potential option is to use QM/MM.

As to which type of model is potentially better to use, it will depend upon how important the metal site is. If, for example, it is involved in something like ligand binding you may well not want to be so constrained as you are with a bonded model. However, for something like a structural metal site, a bonded model might be the best way to go. I’d definitely recommend having a good read about these different types of models and also to which types of sites they are appropriate.