Could protons be used for membrane proteins?

[yongwangCPH]

Hi, I am not sure if this is the right place to ask for help. If not, sorry for this.

Actually I want to titrate a few residues at the TM regions of a membrane protein. I tried but didn't find any good protocol to do it yet. It seems protons is the right tool. I'm considering to prepare the system by CHARMMGUI and AMBERTOOLs, and then run it by OpenMM and protons. But I still have a few concerns:

1) do you think could the charmm36 force field (the only choice in charmmgui as building membrane protein system) be used in protons? If not, do you have any good protocol to prepare such kind of system?

2) I noticed most of CpHMD works are for globular proteins, could the parameters also be used for membrane proteins?

Thanks a lot if you could give any comments.

Yong

[jchodera]

protons is currently still very experimental, though we are hoping to add CHARMM support eventually (with the help of parameters from Benoit Roux). In the meantime, you can check out the constant-pH methodology Benoit Roux has developed for CHARMM here: http://pubs.acs.org/doi/abs/10.1021/acs.jctc.5b00261

[phisanti]

I would like to ask if there has been any progress on the application of protons for membrane protein or explicit solvant simulations. Would it be possible to use the Charmm-GUI or the playmolecule.com framework to build a protein inserted in the membrane and generate the required files and then load then in the simulation? It could work like this:

# Load a protein system
prmtop = app.AmberPrmtopFile('protein.prmtop')
cpin_filename = 'protein.cpin'
water_box = "wat.inp"
ions_env = "ions.inp"

# Assemble system
system = prmtop.createSystem(waterbox=water_box, ions = ions_env, nonbondedMethod=app.NoCutoff, constraints=app.HBonds)
... # Proceed was with the example in https://protons.readthedocs.io/en/latest/modules/simulation%20instructions.html

I would be very keen to know if it would be possible to run something like this.

Kind regards, S