[Chimera-users] Charge assignment to a ligand

[Elaine Meng]

Dear Dr. Prabuddha Bhattacharya, 
You didn't say if you used Chimera to add hydrogens or whether the structures already had hydrogens when they were opened.

If you used Chimera to add hydrogens, it tries to generate states reasonable at neutral pH.  For example, it will not add hydrogens to aspartic acid and glutamic acid side chains of a protein. (If Chimera is adding the -COOH hydrogen, it may be that the atom-type guessing is wrong because the -CO bond lengths are not consistent with a carboxylate group.)

How AddH in Chimera works is explained here:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/addh/addh.html>

However, if your molecules already had the hydrogens on them when they were opened (or fetched from PubChem or by SMILES string), Chimera doesn't delete the hydrogens.... it assumes that is what you want.  You should manually delete the hydrogens you don't want.  Or if it's easier, you could try deleting all hydrogens (e.g. command: delete H) and then adding them back with Chimera, but it may not work the way you want if the bond lengths are not consistent with the negatively charged -COO group.

The force field does not do anything to change protonation states, it just tries to work with what it is given: whatever hydrogens were read in with the structure, or were added in Chimera before charge calculation.

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Apr 13, 2020, at 11:51 AM, Prabuddha Bhattacharya <b.prabuddha3 at gmail.com> wrote:
> 
> Dear Sir,
> 
> I had a query regarding charge assignment to any ligand in chimera. 
> 
> While minimizing the energy of a particular ligand (Tools --> Structure Editing --> Minimize Structure) and also during Dock Prep, I found that for most of the aliphatic and alicyclic amines, they are getting protonated with a residual positive charge; while the aromatic amines remain unprotonated (and hence no residual charge). I understand that this is because of their differential pKb values (basic strengths). 
> 
> On the other side, deprotonation never occurs with the carboxylic acid (-COOH) group.
> 
> Does the Chimera (force fields) control this issue of protonation and deprotonation considering the physiological pH ?
> 
> I will be extremely grateful if some one may kindly clarify my doubts.
> 
> Thanking you in advance,
> 
> With Best Regards,
> 
> Dr. Prabuddha Bhattacharya 
> Dept. Of Chemistry
> Adamas University
> Kolkata 700126
> India
> 
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