I'd like to fold-and-dock a trimeric transmembrane domain. I mostly have the "Fold And Dock" working following the example in demos/public/symmetry_examples/fold-and-dock/. However this is treating the transmembrane helixes as though they are in solvent (so for example any hydrophilic groups always rotate outwards). I'd like to do something which is a combination of "Membrane Abinitio" and "Fold and Dock". Is this possible, and how do I do it?
Can I run membrane_abinitio2.linuxgccrelease app with symmetry options like -symmetry:symmetry_definition etc?
Or, can I pass membrane options like -abinitio:membrane -in:file:lipofile -membrane:Menv_penalties etc to the minirosetta.linuxgccrelease app where -broker:setup is pointing to "CLAIMER FoldandDockClaimer"?
I'm confused about how to combine these two protocols, or if it is even possible to combine them at all. Please let me know the best way to go about this.
I have not tried it and would be surprised if your approach would actually work because you are trying to access 3 different frameworks (membrane abinitio, symmetry, topology broker) in Rosetta that are either pretty old protocols or aren't known to play nicely with other frameworks or each other. Unfortunately, simply adding a new option on the command line does not mean that the underlying code actually works together.
I do have a couple of pointers that should get you started though:
Hope this gets you started, good luck.
Hi Julia - Thank you, I didn't know about RosettaScripts, I'll look into that. Would you recommend RosettaScripts over PyRosetta for this? PyRosetta has been on my to-learn list :)
I read the RosettaMP paper, and tried to walk through the MPsymdock example from the S5 file in the paper. Running into a few issues with that - for the relax step,
rosetta_scripts.static.linuxgccrelease -parser:protocol membrane_relax.xml @relax_flags
[ ERROR ]: Caught exception:
Option matching -membrane_new:setup:spanfiles not found in command line top-level context
For the docking, my Rosetta (2020.11) doesn't have main/source/bin/membrane_symdocking, how would I run that? (Am I running the wrong version?)
The membrane portion of my protein is just a helix, they probably assemble into a homotrimer bundle but I don't know the preferred orientation. Is it possible to simply try every possible orientation and get an energy for it? (eg changing tilt angle in 1 degree steps and rotation in 10 degree steps or similar and then bringing the helixes together starting from each of those orientations)
The executable and options have changed slightly in the updated versions, they are now called
mp_symdock instead of membrane_symdock
-mp:setup:spanfiles instead of -membrane_new:setup:spanfiles
Yes, you should be able to change the orientations, especially if you choose to run things in PyRosetta. Whether you use RosettaScripts or PyRosetta is up to you - it takes a bit longer to learn PyRosetta, but this gives you more flexibility for writing your custom protocols.
Hope this helps,