using Rosetta to compute pH dependent binding?

[Anonymous]

We are interested in creating a protein that will bind to a hormone at physiological pH, but unbind to the hormone at acidic pH, encountered when the complex is cycled through the cell. To do this, we would like to use the pH_mode functionality developed by Kilambi and Gray (Biophys Journal 103:587-595, 2012).

My preliminary attempts to make use of the mode, in Rosetta 3.5, have however proven unsuccessful — the Score energy appears to be constant regardless of what pH value I enter.
Usage of the program is as follows:
score.linuxgccrelease -database database -s complex.pdb -pH_mode true -value_pH 2
vs
score.linuxgccrelease -database database -s complex.pdb -pH_mode true -value_pH 7

Do you know of any changes I should make to properly enable the functionality? I am also curious whether or not PyRosetta has support for pH functions.
Thanks!

[Anonymous]

If Rosetta itself has support for pH functionality, PyRosetta should also have support, as they’re based off the same codebase, and have (almost) all the same functions.

What might be the issue is that Rosetta 3.5 does not have full pH support. Rosetta 3.5 is somewhat old at this point – you may want to try one of the newer weekly releases. (Note that the weeklies go through the same validation procedure as the 3.4 and 3.5 did, they’re just released more frequently. Also note this says more about the extent of validation given to 3.4 and 3.5 than it does about the amount of validation to the weeklies.)

[Anonymous]

Hi rmoretti, Kilambi helped me to use the pH dependent potential in the wk49 release of Rosetta 3.5. It was just a matter of setting f_elec and e_pH to 1 in the talaris weights file, and using the flags -pH_mode true and -value_pH 2.

Do you know how I might call these flags (pH_mode and value_pH) in PyRosetta? Thanks.

[Anonymous]

You’ll need to set them in the options system prior to/with initialization. See http://www.pyrosetta.org/faq#TOC-1.-How-do-I-interact-with-the-Rosetta-Options-system-using-PyRosetta- for details.

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