[Chimera-users] mol2 for NH3

Elaine Meng meng at cgl.ucsf.edu
Thu Jun 11 12:42:37 PDT 2015


Hi Dewey,
The guessing is relatively simple and yes, it does set Chimera atom types so that adding hydrogens will generate protonation states reasonable at pH near 7, as described here:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/addh/addh.html#states>

However, Chimera does not do any sophisticated pKa predictions, it just looks at the functional group itself and tries for the most likely state (for example, negative carboxylates, positive primary amines).  If you are highly concerned with the protonation states, or are working with ligands that might have multiple states, you might want to consider getting your ligand structures from some database like ZINC that has multiple protonation states and allows specifying different pHs instead of doing it all in Chimera from scratch.

NAP is NADP.  We have already  noted that such highly charged molecules are more likely to have problems in addcharge, and in fact we just use lookup tables for ATP, ADP, GTP, and GDP:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/addcharge/addcharge.html#cofactors>
…taken from this database, which also has the various states of NAD and NADP:
<http://www.pharmacy.manchester.ac.uk/bryce/amber/>

You could decide which NADP you want for your docking (or use more than one), and just use the charges from that database.  Although you could apply them in Chimera, that would probably involve a lot of manual editing, so you might just want to manually edit them into your output Mol2 file directly instead of trying to get them in Chimera and then writing  out the Mol2 file.  How to apply custom charges in Chimera is described in the last section of the Add Charge man page, “reading charges from files”:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/addcharge/addcharge.html#input>

The warning message is because the Gasteiger method actually ignores the Chimera net charge guess, as per:
<http://plato.cgl.ucsf.edu/pipermail/chimera-users/2012-March/007336.html>

So the charges you get add up to -4, not -3, which might be the “right” answer anyway.
I hope this clarifies,
Elaine
----------
Elaine C. Meng, Ph.D. 
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Jun 11, 2015, at 11:58 AM, MPI <mpi566 at gmail.com> wrote:
> 
> H Elanine,
> 
>  Thank you for the detailed suggestions. It works.
> 
>> Chimera guessed the most likely charge state as and assigned the nitrogen the atom type of N3+, which would result in 4 hydrogens added and net positive charge.
> 
> I am concerned about the style of  "Chimera guessed" because many
> small molecules and drugs need to be screened.
> 
> When a small molecule is  assigned with  partial charges by the
> command addcharge with am1 method, I noticed that multiple cases
> failed.   With gas method, some cases will pass. However, Chimera gave
> a warning of unequal to the total formal charge (see below).
> 
> What do you think about this ? Is it related to idatmType ?  If so, it
> seems to me that one has to exam each atom of a small molecule if the
> process fails, especially with am1 method.
> 
> Take NAP as example.
> 
> eg,  a warning of net charge
> 
> Adding standard charges
> Charge model: AMBER ff14SB
> 
> Standard charges added
> Assigning partial charges to residue NAP (net charge -3) with gas method
> ....
> ....
> (NAP)          does not equal to the total formal charge (-4.00)
> according to the Gasteiger atom type
> 
> Thanks,
> Dewey




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