openff-toolkit
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openforcefield
Carboxylates from mol2 files produced by tleap have incorrect bond orders and formal charges
Describe the bug Carboxylate functional groups are read incorrectly from mol2 files produced by Amber/tleap. Carboxylate bond orders are specified as 1 such that the total charge of the functional group is -3. The expected total charge is -1 due to resonance states.
To Reproduce
ASP.mol2 is aspartate dipeptide from the OpenFF port of Amber ff14SB, AllDipeptides/MainChain/ASP/ASP.mol2 from AllDipeptides.tar.gz, and was produced from tleap. This file is reproduced below.
@<TRIPOS>MOLECULE
default_name
24 23 1 0 0
SMALL
No Charge or Current Charge
@<TRIPOS>ATOM
1 H1 25.9290 25.1730 24.5000 H 1 ACE 0.112300
2 CH3 25.9910 26.1800 24.0920 C.3 1 ACE -0.366200
3 H2 25.3370 26.8470 24.6490 H 1 ACE 0.112300
4 H3 25.7100 26.1710 23.0410 H 1 ACE 0.112300
5 C 27.4140 26.6690 24.2150 C.2 1 ACE 0.597200
6 O 28.2640 25.9470 24.7160 O.2 1 ACE -0.567900
7 N 27.6440 27.8970 23.7640 N.am 2 ASP -0.516300
8 H 26.8660 28.4410 23.4250 H 2 ASP 0.293600
9 CA 28.9330 28.6030 23.7820 C.3 2 ASP 0.038100
10 HA 29.5120 28.2670 24.6440 H 2 ASP 0.088000
11 CB 29.7230 28.2540 22.5020 C.3 2 ASP -0.030300
12 HB2 29.7230 27.1700 22.3750 H 2 ASP -0.012200
13 HB3 29.2100 28.6900 21.6420 H 2 ASP -0.012200
14 CG 31.1870 28.7210 22.5090 C.2 2 ASP 0.799400
15 OD1 31.6980 29.0740 23.5980 O.co2 2 ASP -0.801400
16 OD2 31.7820 28.7390 21.4100 O.co2 2 ASP -0.801400
17 C 28.6930 30.1240 23.9240 C.2 2 ASP 0.536600
18 O 27.5610 30.5970 23.7680 O.2 2 ASP -0.581900
19 N 29.7400 30.8950 24.2340 N.am 3 NME -0.415700
20 H 30.6470 30.4250 24.2560 H 3 NME 0.271900
21 CH3 29.7000 32.3450 24.3910 C.3 3 NME -0.149000
22 HH31 28.8290 32.6270 24.9840 H 3 NME 0.097600
23 HH32 30.6080 32.6840 24.8890 H 3 NME 0.097600
24 HH33 29.6290 32.8110 23.4080 H 3 NME 0.097600
@<TRIPOS>BOND
1 5 6 2
2 5 7 am
3 2 3 1
4 2 4 1
5 2 5 1
6 1 2 1
7 17 18 2
8 17 19 am
9 14 15 1
10 14 16 1
11 11 12 1
12 11 13 1
13 11 14 1
14 9 10 1
15 9 11 1
This will reproduce the incorrect behavior in python.
from openff.toolkit.topology import Molecule
mol = Molecule.from_file('ASP.mol2')
print(mol.total_charge)
print(mol.to_smiles())
Output
-3.0 e
[H][C@@](C(=O)N([H])C([H])([H])[H])(C([H])([H])[C-]([O-])[O-])N([H])C(=O)C([H])([H])[H]
Computing environment
- Operating system: Ubuntu 20.04.2
- Output of running
conda list
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xorg-libxdmcp 1.1.3 h7f98852_0 conda-forge
xorg-libxext 1.3.4 h7f98852_1 conda-forge
xorg-libxrender 0.9.10 h7f98852_1003 conda-forge
xorg-libxt 1.2.1 h7f98852_2 conda-forge
xorg-renderproto 0.11.1 h7f98852_1002 conda-forge
xorg-xextproto 7.3.0 h7f98852_1002 conda-forge
xorg-xproto 7.0.31 h7f98852_1007 conda-forge
xz 5.2.5 h516909a_1 conda-forge
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zipp 3.6.0 pyhd8ed1ab_0 conda-forge
zlib 1.2.11 h36c2ea0_1013 conda-forge
zstd 1.5.0 ha95c52a_0 conda-forge
Additional context Reading carboxylate-containing mol2 files produced by tleap into OpenEye also produces an incorrect molecule with a total charge of -3. After writing the OpenEye molecule to SDF, the carboxylate bond orders are 5.
This problem and a solution are discussed in this issue from amber-ff-porting, but this problem in not documented in the OpenFF toolkit.
Thanks @chapincavender for reporting this and linking to the issue on amber-ff-porting.
I'm not sure what action to take on this - mol2 is famously lacking specification and these two tools clearly have different interpretations of the molecule in the file. Documentation of this ambiguity may be good, and in the future we could have [C-]([O-])([O-]) motifs lead to an informative error.
in the future we could have
[C-]([O-])([O-])motifs lead to an informative error.
I think this is the best way to address this in the long run. Throw a warning or error that this chemistry is unlikely but is known to show up in molecules produced by this pathway.