[Chimera-users] mol2 for NH3

Elaine Meng meng at cgl.ucsf.edu
Thu Jun 11 15:45:31 PDT 2015


As mentioned previously, there is a high incidence of charge-calculation failure for such highly charged molecules, and as you saw, the AM1 method depends on the coordinates of the atoms (the 3D structure), not just the bond connectivity like Gasteiger.  Thus even the same exact molecule in different conformations could have different results. 

Thus, no use in asking me whether it will work on your specific molecule… you’d have to try and find out.  I don’t know the explanation.

 Also, keep in mind that Antechamber is a separate program from Chimera (developed by a separate group, although included with and used by Chimera) and that it is not mean to handle all possible molecules.  From <http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/addcharge/addcharge.html>:

"Note that Antechamber/GAFF are meant to handle most small organic molecules, but not metal complexes, inorganic compounds, or unstable species such as radicals, and may not work well on highly charged molecules."

I would not say that ignoring the guess is the reason why Gasteiger works.  Gasteiger is just simpler than the other method (more “quick-n-dirty”).  Maybe you could conclude it was at least partly the reason if AM1 works when you change the guess to -4 from -3, but I don’t know if you did that.

Best,
Elaine

> On Jun 11, 2015, at 3:31 PM, MPI <mpi566 at gmail.com> wrote:
> 
> Hi Elaine,
> 
>    Thank you very much for the explanations. It is clear to me why
> gas method works by ignoring the calculation of net charge in Chimera.
> 
> I also noticed that Eric mentioned ligand preparation for FAD or NAD
> and provided scripts eg, dockprep.py through DockPrep in Chimera  to
> generate mol2 but it fails for some cases of drugs/small molecules
> when it uses am1 method and gets choked with sqm.
> 
> Can you explain two examples as it fails for NADP from PDB 1w6u
> but succeeds for NAD from PDB 2h4f  ?    Of course, it works well for
> both, using gas method.
> 
> Can  a mol2 file of NADP be generated "with am1 method"  by Chimera  ?
> 
> Thanks,
> Dewey
> 
> # Here are  the NADP coordinates prepared from PDB 1w6u.
> HETATM 8621  O4B NAP A1329      27.294   6.186  24.430  1.00 31.96           O
> HETATM 8622  C3B NAP A1329      29.273   7.323  24.965  1.00 31.96           C
> HETATM 8623  O3B NAP A1329      29.117   8.708  24.774  1.00 31.54           O
> HETATM 8624  C2B NAP A1329      28.635   6.867  26.257  1.00 31.84           C
> HETATM 8625  O2B NAP A1329      28.669   7.864  27.246  1.00 32.77           O
> HETATM 8626  C1B NAP A1329      27.211   6.566  25.797  1.00 31.30           C
> HETATM 8627  N9A NAP A1329      26.569   5.508  26.595  1.00 29.72           N
> HETATM 8628  C8A NAP A1329      26.965   4.203  26.733  1.00 29.33           C
> HETATM 8629  N7A NAP A1329      26.094   3.560  27.542  1.00 29.19           N
> HETATM 8630  C5A NAP A1329      25.141   4.438  27.924  1.00 29.33           C
> HETATM 8631  C6A NAP A1329      24.024   4.317  28.742  1.00 29.04           C
> HETATM 8632  N6A NAP A1329      23.810   3.204  29.446  1.00 28.84           N
> HETATM 8633  N1A NAP A1329      23.221   5.420  28.943  1.00 27.78           N
> HETATM 8634  C2A NAP A1329      23.512   6.631  28.345  1.00 28.64           C
> HETATM 8635  N3A NAP A1329      24.622   6.744  27.534  1.00 29.91           N
> HETATM 8636  C4A NAP A1329      25.422   5.665  27.329  1.00 30.00           C
> HETATM 8637  O1N NAP A1329      31.899   5.159  18.612  1.00 31.81           O
> HETATM 8638  O2N NAP A1329      30.918   7.458  19.154  1.00 31.66           O
> HETATM 8639  O5D NAP A1329      29.461   5.537  18.415  1.00 31.27           O
> HETATM 8640  C5D NAP A1329      28.309   6.346  18.394  1.00 29.19           C
> HETATM 8641  C4D NAP A1329      27.184   5.571  17.700  1.00 28.26           C
> HETATM 8642  O4D NAP A1329      27.552   5.194  16.382  1.00 27.30           O
> HETATM 8643  C3D NAP A1329      26.819   4.284  18.421  1.00 28.15           C
> HETATM 8644  O3D NAP A1329      25.416   4.141  18.367  1.00 27.49           O
> HETATM 8645  C2D NAP A1329      27.461   3.193  17.600  1.00 27.46           C
> HETATM 8646  O2D NAP A1329      26.705   2.021  17.677  1.00 27.27           O
> HETATM 8647  C1D NAP A1329      27.438   3.801  16.202  1.00 27.15           C
> HETATM 8648  N1N NAP A1329      28.517   3.306  15.333  1.00 27.66           N
> HETATM 8649  C2N NAP A1329      29.780   3.831  15.412  1.00 28.55           C
> HETATM 8650  C3N NAP A1329      30.781   3.348  14.576  1.00 30.27           C
> HETATM 8651  C7N NAP A1329      32.172   3.917  14.648  1.00 31.70           C
> HETATM 8652  O7N NAP A1329      33.086   3.524  13.659  1.00 32.49           O
> HETATM 8653  N7N NAP A1329      32.510   4.759  15.629  1.00 31.91           N
> HETATM 8654  C4N NAP A1329      30.499   2.342  13.655  1.00 30.48           C
> HETATM 8655  C5N NAP A1329      29.207   1.820  13.569  1.00 29.50           C
> HETATM 8656  C6N NAP A1329      28.227   2.325  14.423  1.00 29.09           C
> HETATM 8657  P2B NAP A1329      28.809   7.452  28.801  1.00 33.99           P
> HETATM 8658  O1X NAP A1329      29.948   6.524  28.942  1.00 33.70           O
> HETATM 8659  O2X NAP A1329      29.037   8.749  29.590  1.00 34.45           O
> HETATM 8660  O3X NAP A1329      27.518   6.755  29.259  1.00 32.91           O
> HETATM 8661  PA ANAP A1329      31.539   5.835  21.912  0.50 35.79           P
> HETATM 8662  O1AANAP A1329      32.626   4.830  21.987  0.50 36.39           O
> HETATM 8663  O2AANAP A1329      32.125   7.258  21.784  0.50 34.61           O
> HETATM 8664  O5BANAP A1329      30.638   5.689  23.240  0.50 34.77           O
> HETATM 8665  C5BANAP A1329      29.241   5.476  23.204  0.50 33.46           C
> HETATM 8666  C4BANAP A1329      28.496   6.644  23.846  0.50 32.43           C
> HETATM 8667  O3 ANAP A1329      30.551   5.483  20.682  0.50 34.18           O
> HETATM 8668  PN ANAP A1329      30.815   5.984  19.171  0.50 31.74           P
> 
> 
> 
> 
> On 6/11/15, Elaine Meng <meng at cgl.ucsf.edu> wrote:
>> 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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