Hi everyone,
I would like to study a protein that has an oxygen molecule in the structure. In particular, it’s an oxygen molecule in a copper coordination site, so I think it’s important to be considered during the simulation. I’m working with charmm36 ff but I don’t understand how I can simulate also the oxygen. Using the residue name “OXY” I obtain the error: “Residue ‘OXY’ not found in residue topology database”. Looking at the atom types recognized by the force field I didn’t see anything related to molecular oxygen (I checked the .rtp files in the force field folder, do I have to check something else?). Am I working correctly? Which is the best way to work with a protein containing an oxygen molecule in the structure?
Thank you very much,
CHARMM36 includes an O2 residue for molecular oxygen (in aminoacids.rtp), but it is specifically for use in the context of ligating to heme, so it has partial charge assignments reflecting that coordination. For your case, you would have to reparametrize a new entity that has charge assignment reflecting coordination to copper.
Thank you for the answer, now I have a question but I’m not sure if it’s relevant. After your answer, I checked again in the literature and I found a paper about a molecular dynamics simulation study on the same protein as my simulation and they talked about charges assigned to the copper ions and the oxygen atoms. In particular, the charges they talked about were retrieved from quantum chemical calculations performed using TeraChem. I’m not an expert so I’m not sure if they could be the same charges you talked about, probably not so I’m sorry.
Until now I thought that for the copper ions would be ok to consider them with a +2 charge but from the paper it seems it’s not like that. At this point, my doubt is: are the quantum chemical calculations the best way to proceed or is it correct also to use the charges for the ions taking them from the ff parameters?
Furthermore, assuming that I have to use the charges I’ve found in this paper to reparametrize a new entity for an oxygen molecule coordinating copper, they are -0.5083 and -0.5308, and in the neutralization step, I have a system with non-integer charge. How am I supposed to neutralize this system?
In addition to searching in the literature, I don’t know how to reparametrize a new entity representing an oxygen molecule coordinating copper. Do I have to use some particular tool? Thank you very much.
Most ions like this are assigned a +2 charge for simplicity. QM calculations show this clearly isn’t the case because charge is delocalized among ligating residues, but our MM force fields aren’t parametrized to model this unless you reparametrize those residues, too. Stick with an ion of +2 charge and that will be consistent with most publications. It’s a crude approximation but there are limits to what fixed-charge MM modeling can do.
Without context I can’t say why those charges were assigned the way they were, but if you do not get a system with an integer charge, it’s physically nonsensical. Make sure there weren’t other aspects of the coordination complex with reassigned charges that make everything end up being a whole number.
You have to be well versed in the methods underlying the force field you’re using. The approach varies by force field. And dealing with transition metals is honestly kind of a nightmare. Most parameters out there are pretty crude approximations, as noted above. Some are even just chemical intuition, sadly enough.