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The question about  protonation of Rosetta

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The question about  protonation of Rosetta

I want to manually set  protonation of residues.

 I find  there are params in Rosetta database folder

 ASP_P1.params ASP_P2.params

GLU_P1.params GLU_P2.params

What are differences between ASP_P1.params and  ASP_P2.params,  and GLU_P1.params and GLU_P2.params ?

In additon,  HIS  has   two deprotonation states, HID and HIE, why there are only  one file HIS_P.params ?

The above problem pluzzes me for a long time,


Post Situation: 
Tue, 2017-12-19 05:44

For ASP_P1/ASP_P2 and GLU_P1/GLU_P2 the difference is which atom the proton is put onto. For regular, deprotonated ASP/GLU, due to resonance, the two carboxylate oxygens are chemically identical. As such, much of Rosetta sampling doesn't bother to try to "flip" the carboxylate. However, once you add a proton to the residues, the two oxygens become distinct - one is a hydroxyl, and one is a carbonyl.  That's what the difference between the P1 and P2 patches are. For ASP_P1.params, the OD2 atom is the hydroxyl oxygen, and the ASP_P2.params has OD1 being the hydroxyl oxygen (similar for GLU). Between the two of them you can effectively sample all the orientations of the hydroxyl in the protonated state of the residue.

For HIS_P, this is the *protonated* version - that is, with both nitrogens having protons on them. The default protonation state for HIS in Rosetta is the neutral, single proton state. The "HIE" and "HID" singly protonated versions are the standard HIS.params and HIS_D.params files, respectively. These are both active by default, and Rosetta automatically picks the correct tautomer residue type based on the surrounding environment, and which one is the lowest energy.

Tue, 2017-12-19 07:40

Thanks a lot, I understand the differences now.

My pH of environment was 5.5.
I use H++ and PROPKA software, and they tell me the protonation state of catalytic pocket residue. 
His557 was HIP, His516 was HIE.
In the other hand,  Asp526 (within 5A of catalytic pocket) is ASH.

I want to relax the protein, dock the protein with a small molecule, and then design the catalytic pocket.
But after relaxing, I find the bottom of PDB shows His557 is HIS and Asp526 is ASP.

1. If  I manually set  protonation of Asp526 with -extra_res_fa, can I randomly  set with  ASP_P1 as well as ASP_P2 ?

2. I relax with -value_pH 5.5, and the result of protonation states are differences from H++ and PROPKA, 

Is my option false? And can relax at pH 5.5 automatically?

3. If  I manually set HID, which HIS_D.params should I modify, many file folders  have HIS_D.params which are difference.

Wed, 2017-12-20 19:53

1) The option -extra_res_fa only tells Rosetta what the chemical structure of a residue is like -- it doesn't actually tell Rosetta to use it. To tell Rosetta to model something as a different residue, you'll need to alter the input PDB to use the appropriate three letter code that specifies that residue. (What three letter code to be used should be specified by the IO_STRING line in the params file.)

2) The `-value_pH` option isn't recognized generally by Rosetta. This is an option which is specific to Rosetta's pH mode. (Specifically, it's used by the e_pH score term. I'm not too familiar with this - see for more details.)  -- In particular, it doesn't allow you to automatically set the chemical protonation state during a regular relax runs.

3) HIS is special cased such that HIS_D is automatically sampled. There's nothing you have to change - Rosetta considers both HIE and HID tautomers, and picks whichever one it thinks is best. There's not really a way to force it to only use one. (Well, unless you make a new Residue type which only takes the one tautomer -- but that's probably not what you want to do.)

Mon, 2018-01-15 15:34