[Chimera-users] Ionisation state of ligand and protein residues processed with chimera

[Elaine Meng]

Dear Tao,
Chimera AddH does not have the option to predict protonation state for different pH values, but you can do it using a different tool in Chimera to add hydrogens:  menu Tools… Structure Editing… PDB2PQR, or command "pdb2pqr".  In the graphical interface opened from the menu, click the triangle next to "Options" to show the options:

Use PROPKA to predict protonation states: change to "true"
pH value to use with PROPKA: default 7, you can change to the pH you want

See documentation for more information:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/apbs/pdb2pqr.html>
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/midas/pdb2pqr.html>

Then Apply or OK will run the calculation using a web service at the NBCR.  One thing that might be confusing is that the result is opened as a new model in Chimera (i.e. original could be model 0, results will be model 1 so that there are two copies of the structure open in Chimera).  PDB2PQR also assigns charges but the choices are different from Chimera's Add Charge (except for PDB2PQR AMBER and Add Charge AMBER ff99SB, AMBER ff99bsc0 all give the same charges).

Depending on which charges you want, you could try running Dock Prep before or after PDB2PQR.  If you run Dock Prep after, make sure to do it on the PDB2PQR results (model 1 in my example) and turn off the "add hydrogens" option because you want only the hydrogens from PDB2PQR.  There might be errors, however, because PDB2PQR sometimes generates hydrogen names that are not recognized by the Add Charge step of Dock Prep… you may have to re-name some N-terminal -NH3+ hydrogen(s) from H to H1 to get it to run without error.

Or, you could do the pKa prediction outside of Chimera using some other program, for example:

H++ web server (this also adds the hydrogens)
http://biophysics.cs.vt.edu/

PROPKA web server (this just predicts the pKa of each ionizable sidechain, and then you would use this information in combination with your desired pH to add hydrogens with Chimera or some other program):
http://propka.ki.ku.dk/

That PROPKA program is the same one that the PDB2PQR server uses.  I hope this helps,
Elaine
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Elaine C. Meng, Ph.D. 
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco

On May 14, 2014, at 6:27 PM, 崔涛 <cuitao at mail.hzau.edu.cn> wrote:

> Dear Elaine
> Thanks very much for your quick reply which helped me a lot.
> The documentation mentions “AddH aims to generate protonation states reasonable at physiological pH”. Now I have a new question. Is there a way and how to generate protonation states reasonable at other pH (such as 6.0 or 8.0) with chimera? I have found options to specify different tautomers in chimera. However, I didn’t find options for changing pH.
> Best regards,
> Tao