Explicit valence for atom # 18 N, 4, is greater than permitted

[emainas]

Hi everyone, I am simply doing ligand_off_molecule = Molecule.from_file("molecule.sdf", file_format='sdf')
where my molecule has a positive charge on nitrogen 19 (18 if you start counting from 0) and I do not know how to pass it properly. I attach my molecule.sdf file. I added the flag "M CHG 1 19 1" at the end but it does not work. Any ideas?

[emainas]

I am not sure my file got pasted here. I add it here again

new
  -ISIS-            3D

 78 81  0  0  0  0  0  0  0  0  0
   44.4530   84.8580   23.7330 N   0  0  0  0  0
   44.3400   84.1110   24.4020 H   0  0  0  0  0
   45.1030   84.6780   22.5520 C   0  0  0  0  0
   45.0740   86.0120   21.9230 C   0  0  0  0  0
   44.4070   86.9160   22.7410 C   0  0  0  0  0
   44.0190   86.1480   23.9010 C   0  0  0  0  0
   45.7680   86.2120   20.5950 C   0  0  0  0  0
   46.5160   85.4330   20.4060 H   0  0  0  0  0
   46.2930   87.1740   20.5680 H   0  0  0  0  0
   45.0470   86.1880   19.7700 H   0  0  0  0  0
   45.5960   83.6350   22.1480 O   0  0  0  0  0
   44.1750   88.3500   22.5040 C   0  0  0  0  0
   44.0220   88.9660   23.3930 H   0  0  0  0  0
   44.1190   88.9460   21.2890 C   0  0  0  0  0
   43.9360   90.0180   21.2030 H   0  0  0  0  0
   44.2260   88.3900   20.3600 H   0  0  0  0  0
   43.3340   86.6150   24.9990 C   0  0  0  0  0
   43.0790   87.6680   24.9400 H   0  0  0  0  0
   43.0070   84.6780   26.4310 N   0  0  0  0  0
   43.3680   83.9770   25.8000 H   0  0  0  0  0
   42.8860   85.9810   26.2410 C   0  0  0  0  0
   42.3100   86.6850   27.3430 C   0  0  0  0  0
   42.0740   85.7470   28.3110 C   0  0  0  0  0
   42.5140   84.5180   27.7130 C   0  0  0  0  0
   42.0530   88.1740   27.3690 C   0  0  0  0  0
   41.4470   88.4810   26.5080 H   0  0  0  0  0
   42.9950   88.7340   27.3390 H   0  0  0  0  0
   41.5110   88.4820   28.2700 H   0  0  0  0  0
   42.4830   83.2880   28.3400 C   0  0  0  0  0
   42.1460   83.3110   29.3740 H   0  0  0  0  0
   42.7350   81.5480   26.5380 N   0  0  0  0  0
   42.4470   82.1650   25.7940 H   0  0  0  0  0
   42.8170   81.9440   27.8690 C   0  0  0  0  0
   43.2220   80.8330   28.5650 C   0  0  0  0  0
   43.3940   79.7630   27.6420 C   0  0  0  0  0
   43.0740   80.2070   26.3820 C   0  0  0  0  0
   43.8330   78.3560   27.9880 C   0  0  0  0  0
   44.1580   78.2600   29.0290 H   0  0  0  0  0
   44.6750   78.0440   27.3580 H   0  0  0  0  0
   43.0150   77.6430   27.8310 H   0  0  0  0  0
   43.0460   79.4490   25.1280 C   0  0  0  0  0
   43.3810   78.4240   25.2680 H   0  0  0  0  0
   42.2470   80.9250   23.3250 N   0  0  0  0  0
   42.0660   81.7680   23.8440 H   0  0  0  0  0
   42.7120   79.7320   23.8200 C   0  0  0  0  0
   42.7780   78.7990   22.7240 C   0  0  0  0  0
   42.3490   79.4830   21.5930 C   0  0  0  0  0
   42.0020   80.8730   21.9860 C   0  0  0  0  0
   43.2230   77.3550   22.8140 C   0  0  0  0  0
   42.9530   76.7790   21.9230 H   0  0  0  0  0
   42.7560   76.8500   23.6670 H   0  0  0  0  0
   44.3100   77.2900   22.9380 H   0  0  0  0  0
   41.5900   81.8050   21.3110 O   0  0  0  0  0
   42.2470   78.9630   20.2180 C   0  0  0  0  0
   42.7130   77.9890   20.0650 H   0  0  0  0  0
   41.6460   79.5560   19.1630 C   0  0  0  0  0
   41.6280   79.0780   18.1820 H   0  0  0  0  0
   41.1460   80.5220   19.2260 H   0  0  0  0  0
   43.4670   80.7580   30.0570 C   0  0  0  0  0
   42.3260   80.0500   30.8310 C   0  0  0  0  0
   41.0140   80.8430   30.7690 C   0  0  0  0  0
   40.8530   81.7740   31.7420 O   0  0  0  0  0
   40.1900   80.7240   29.8780 O   0  0  0  0  0
   43.6180   81.7620   30.4720 H   0  0  0  0  0
   44.4070   80.2270   30.2490 H   0  0  0  0  0
   42.6570   79.9520   31.8710 H   0  0  0  0  0
   42.1640   79.0570   30.3970 H   0  0  0  0  0
   41.6320   81.6800   32.3500 H   0  0  0  0  0
   41.4780   85.9580   29.6870 C   0  0  0  0  0
   39.9640   85.6330   29.7220 C   0  0  0  0  0
   39.3500   85.9600   31.0890 C   0  0  0  0  0
   39.4030   85.2100   32.0490 O   0  0  0  0  0
   38.7750   87.1830   31.1990 O   0  0  0  0  0
   42.0010   85.3430   30.4290 H   0  0  0  0  0
   41.6350   86.9940   30.0110 H   0  0  0  0  0
   39.4800   86.2220   28.9340 H   0  0  0  0  0
   39.8310   84.5640   29.5210 H   0  0  0  0  0
   38.8610   87.6120   30.3090 H   0  0  0  0  0
  1  2  1  0  0  0
  1  3  1  0  0  0
  1  6  1  0  0  0
  3  4  1  0  0  0
  3 11  2  0  0  0
  4  5  2  0  0  0
  4  7  1  0  0  0
  5  6  1  0  0  0
  5 12  1  0  0  0
  6 17  2  0  0  0
  7  8  1  0  0  0
  7  9  1  0  0  0
  7 10  1  0  0  0
 12 13  1  0  0  0
 12 14  2  0  0  0
 14 15  1  0  0  0
 14 16  1  0  0  0
 17 18  1  0  0  0
 17 21  1  0  0  0
 19 20  1  0  0  0
 19 21  2  0  0  0
 19 24  1  0  0  0
 21 22  1  0  0  0
 22 23  2  0  0  0
 22 25  1  0  0  0
 23 24  1  0  0  0
 23 69  1  0  0  0
 24 29  2  0  0  0
 25 26  1  0  0  0
 25 27  1  0  0  0
 25 28  1  0  0  0
 29 30  1  0  0  0
 29 33  1  0  0  0
 31 32  1  0  0  0
 31 33  1  0  0  0
 31 36  1  0  0  0
 33 34  2  0  0  0
 34 35  1  0  0  0
 34 59  1  0  0  0
 35 36  2  0  0  0
 35 37  1  0  0  0
 36 41  1  0  0  0
 37 38  1  0  0  0
 37 39  1  0  0  0
 37 40  1  0  0  0
 41 42  1  0  0  0
 41 45  2  0  0  0
 43 44  1  0  0  0
 43 45  1  0  0  0
 43 48  1  0  0  0
 45 46  1  0  0  0
 46 47  2  0  0  0
 46 49  1  0  0  0
 47 48  1  0  0  0
 47 54  1  0  0  0
 48 53  2  0  0  0
 49 50  1  0  0  0
 49 51  1  0  0  0
 49 52  1  0  0  0
 54 55  1  0  0  0
 54 56  2  0  0  0
 56 57  1  0  0  0
 56 58  1  0  0  0
 59 60  1  0  0  0
 59 64  1  0  0  0
 59 65  1  0  0  0
 60 61  1  0  0  0
 60 66  1  0  0  0
 60 67  1  0  0  0
 61 62  1  0  0  0
 61 63  2  0  0  0
 62 68  1  0  0  0
 69 70  1  0  0  0
 69 74  1  0  0  0
 69 75  1  0  0  0
 70 71  1  0  0  0
 70 76  1  0  0  0
 70 77  1  0  0  0
 71 72  2  0  0  0
 71 73  1  0  0  0
 73 78  1  0  0  0
M  CHG  1   19   1
M  END

[j-wags]

Thanks for writing in - I've reproduced the error and am working to get to the bottom of it.

[j-wags]

Still looking into this, it's got something to do with having this nitrogen be the only one in the molecule with an explicit double bond.

[j-wags]

Looking at the canonical structure of biliverdin (which this either is, or is very similar to), it appears that only three of the pyrrole groups should be protonated. I don't have an editor close at hand that could modify this, but if you do @emainas, could you try deprotonating the nitrogen with the explicit double bond and see if that clears it up?

[emainas]

yes it works without the proton but I want to study different protonation states, one of which is the structure with all 4 rings protonated. why would it not work though? all the valencies look good (unless I am missing sth?).

[mattwthompson]

(Is protomer synonymous with protonation state? I forget a lot of cheminformatics jargon, disregard if I'm confused)

The toolkit provides Molecule.enumerate_protomers which could serve as programmatic bridge between molecules' less exotic forms and their protonation states, each of which can be roundtripped with disk and other representations

>>> from openff.toolkit import Molecule
>>> bill = Molecule.from_inchi("InChI=1S/C33H34N4O6/c1-7-20-19(6)32(42)37-27(20)14-25-18(5)23(10-12-31(40)41)29(35-25)15-28-22(9-11-30(38)39)17(4)24(34-28)13-26-16(3)21(8-2)33(43)36-26/h7-8,13-15,35H,1-2,9-12H2,3-6H3,(H,36,43)(H,37,42)(H,38,39)(H,40,41)/b26-13-,27-14-,28-15-")
>>> for index, protomer in enumerate(bill.enumerate_protomers()):
...     protomer.to_file(f"protomer{index}.sdf", file_format="sdf")
...     Molecule.from_file(f"protomer{index}.sdf", file_format="sdf").n_atoms
...
75
76
76
77

[j-wags]

Thanks for checking on the deprotonated form, @emainas. My big-conjugated-molecules knowledge is a little rusty but I'm inclined to think (4/10) that the fully protonated form is chemically valid. Could you share how you made the structure in this report (namely, was the kekule structure hand-drawn, or interpreted by some tool? This will help me debug)

Matt - I think the issue is with RDKit file I/O specifically. Since your code block runs enumerate_protomers successfully, it means that it's using OpenEye for that (and thereofre also for file I/O)

[emainas]

@mattwthompson I suspect that this is the protomers of the propionic tails. biliverdin is technically a tetrapyrrolic di-acid because of the two tails so I guess your code generated the atom numbers for

1. doubly deprotonated - 75
2. proton on the left tail only - 76
3. proton on the right - 76
4. proton on both - 77

and I believe that all 4 of these protomers refer to the same version of the ring system where 3 out of 4 rings are protonated. nevertheless the snippet you attached actually comes super handy for stuff I work on so thanks for that

@j-wags I have a pdb (I don't remember where I got it initially - I think from some biliprotein in the PDBdatabank) that I then edited manually to get the nomenclature correct. next I opened it with pymol and added the +1 charge on the 4th (normally deprotonated) ring. I attach the pdb file I had before and after the pymol proton addition. I might have created a monster of an sdf file with all this editing and converting. see the attached pdb (the extra proton I added with pymol is
HETATM 79 HB TPS 1 43.368 83.977 25.800 0.00 0.00 H) -
twohydro.pdb.zip

question: what is the proper way to generate the sdf file? with amber only mol2 files are needed instead of sdf for ligands.

[j-wags]

I went down so many rabbit holes, and I think I found the issues in the funniest possible place.

In the final line of the original file, you have M CHG 1 19 1. Could you remove one space between the first 1 and the 19? That gets it to load for me. (it's due to the use of fixed-width columns, see the page marked 49 in the spec for details)