Parametrization error

[matteo-ambrosetti]

Hello everyone,
I am trying to perform an MD of betaine in water but seems that it is not possible for openforcefield to get the parameters of the solute.

I get the following warning:
Warning: In AmberToolsToolkitwrapper.compute_partial_charges_am1bcc: Molecule '' has more than one conformer, but this function will only generate charges for the first one.

But the problem is the following error:

---------------------------------------------------------------------------
CalledProcessError                        Traceback (most recent call last)
<ipython-input-5-5939983b4e9d> in <module>
    44 
    45 # Parametrize the topology and create an OpenMM System.
---> 46 system = forcefield.create_openmm_system(off_topology)
    47 
    48 # Create the integrator to do Langevin dynamics

~/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/typing/engines/smirnoff/forcefield.py in create_openmm_system(self, topology, **kwargs)
  1136         # Add forces and parameters to the System
  1137         for parameter_handler in parameter_handlers:
-> 1138             parameter_handler.create_force(system, topology, **kwargs)
  1139 
  1140         # Let force Handlers do postprocessing

~/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/typing/engines/smirnoff/parameters.py in create_force(self, system, topology, **kwargs)
  2925             toolkit_registry = kwargs.get('toolkit_registry', GLOBAL_TOOLKIT_REGISTRY)
  2926             temp_mol.generate_conformers(n_conformers=10, toolkit_registry=toolkit_registry)
-> 2927             temp_mol.compute_partial_charges_am1bcc(toolkit_registry=toolkit_registry)
  2928 
  2929             # Assign charges to relevant atoms

~/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/topology/molecule.py in compute_partial_charges_am1bcc(self, toolkit_registry)
  2301             charges = toolkit_registry.call(
  2302                       'compute_partial_charges_am1bcc',
-> 2303                       self
  2304             )
  2305         elif isinstance(toolkit_registry, ToolkitWrapper):

~/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/utils/toolkits.py in call(self, method_name, *args, **kwargs)
  3660                 method = getattr(toolkit, method_name)
  3661                 try:
-> 3662                     return method(*args, **kwargs)
  3663                 except NotImplementedError:
  3664                     pass

~/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/utils/toolkits.py in compute_partial_charges_am1bcc(self, molecule)
  3189                 subprocess.check_output([
  3190                     "antechamber", "-i", "charged.mol2", "-fi", "mol2", "-o", "charges2.mol2", "-fo", "mol2", "-c", "wc", "-cf",
-> 3191                     "charges.txt", "-pf", "yes"
  3192                 ])
  3193                 #os.system('cat charges.txt')

~/anaconda3/envs/openmm/lib/python3.7/subprocess.py in check_output(timeout, *popenargs, **kwargs)
   409 
   410     return run(*popenargs, stdout=PIPE, timeout=timeout, check=True,
--> 411                **kwargs).stdout
   412 
   413 

~/anaconda3/envs/openmm/lib/python3.7/subprocess.py in run(input, capture_output, timeout, check, *popenargs, **kwargs)
   510         if check and retcode:
   511             raise CalledProcessError(retcode, process.args,
--> 512                                      output=stdout, stderr=stderr)
   513     return CompletedProcess(process.args, retcode, stdout, stderr)
   514 

CalledProcessError: Command '['antechamber', '-i', 'charged.mol2', '-fi', 'mol2', '-o', 'charges2.mol2', '-fo', 'mol2', '-c', 'wc', '-cf', 'charges.txt', '-pf', 'yes']' returned non-zero exit status 1.

Could it be caused by the dimension of the molecule?

To reproduce the error:

import simtk.openmm as omm
import simtk.openmm.app as app
import simtk.unit as unit
import openforcefield.topology as off_top
from openforcefield.typing.engines.smirnoff import ForceField
import numpy as np

# Read input geometry
pdbfile = app.PDBFile("betaine.pdb")
omm_topology = pdbfile.topology

# Betaine 30
solute = off_top.Molecule.from_smiles('C1=CC=C(C=C1)C2=CC(=[N+](C(=C2)C3=CC=CC=C3)C4=CC(=C(C(=C4)C5=CC=CC=C5)[O-])C6=CC=CC=C6)C7=CC=CC=C7')

# System
all_system = [solute]

# Create the Open Force Field Topology from an OpenMM Topology object.
off_topology = off_top.Topology.from_openmm(openmm_topology=omm_topology, unique_molecules=all_system)

# Load the OpenFF "Parsley" force field.
forcefield = ForceField('openff-1.1.0.offxml')

# Parametrize the topology and create an OpenMM System.
system = forcefield.create_openmm_system(off_topology)

betaine.zip

[mattwthompson]

Hi, thanks for the bug report. There are a few things that could be the cause of this

• Molecule may be too big for antechamber - unlikely; 43 heavy atoms shouldn't be too much
• Molecule may have too many rings - also unlikely, although I don't have much intuition here
• Something may quirky with a different version of AmberTools

I'm unable to reproduce this on my machine using your snippet, although I may not be using the most up-to-date dependencies or the same ones as you are. Could you show the output of conda list?

[matteo-ambrosetti]

Thanks @mattwthompson,
here is the output of conda list

# Name                    Version                   Build  Channel
_libgcc_mutex             0.1                        main
acpype                    20200315132700           pypi_0    pypi
ambertools                18.0                          0    omnia
ase                       3.19.1                     py_0    conda-forge
attrs                     19.3.0                     py_0    conda-forge
backcall                  0.1.0                      py_0    conda-forge
biopython                 1.76             py37h516909a_0    conda-forge
blas                      1.0                         mkl
bleach                    3.1.4              pyh9f0ad1d_0    conda-forge
bzip2                     1.0.8                h7b6447c_0
ca-certificates           2020.4.5.1           hecc5488_0    conda-forge
cairo                     1.14.12              h8948797_3
certifi                   2020.4.5.1       py37hc8dfbb8_0    conda-forge
cftime                    1.1.1.2          py37h03ebfcd_0    conda-forge
chemper                   1.0.0+1.g3e54eb4          pypi_0    pypi
click                     7.1.1              pyh8c360ce_0    conda-forge
curl                      7.68.0               hf8cf82a_0    conda-forge
cycler                    0.10.0                     py_2    conda-forge
cython                    0.29.15          py37he6710b0_0
dbus                      1.13.6               he372182_0    conda-forge
decorator                 4.4.2                      py_0    conda-forge
defusedxml                0.6.0                      py_0    conda-forge
entrypoints               0.3             py37hc8dfbb8_1001    conda-forge
expat                     2.2.9                he1b5a44_2    conda-forge
fftw3f                    3.3.4                         2    omnia
flask                     1.1.2              pyh9f0ad1d_0    conda-forge
fontconfig                2.13.0               h9420a91_0
freetype                  2.9.1                h8a8886c_1
glib                      2.63.1               h5a9c865_0
griddataformats           0.5.0                      py_0    conda-forge
gsd                       2.1.0            py37hc1659b7_0    conda-forge
gst-plugins-base          1.14.5               h0935bb2_2    conda-forge
gstreamer                 1.14.5               h36ae1b5_2    conda-forge
hdf4                      4.2.13                        0    conda-forge
hdf5                      1.10.4          nompi_h3c11f04_1106    conda-forge
icu                       58.2                 h9c2bf20_1
importlib-metadata        1.5.2            py37hc8dfbb8_0    conda-forge
importlib_metadata        1.5.2                         0    conda-forge
intel-openmp              2020.0                      166
iodata                    0.1.7            py37h035aef0_0    theochem
ipykernel                 5.2.0            py37h43977f1_1    conda-forge
ipython                   7.13.0           py37hc8dfbb8_2    conda-forge
ipython_genutils          0.2.0                      py_1    conda-forge
ipywidgets                7.5.1                      py_0    conda-forge
itsdangerous              1.1.0                      py_0    conda-forge
jedi                      0.16.0           py37hc8dfbb8_1    conda-forge
jinja2                    2.11.1                     py_0    conda-forge
joblib                    0.14.1                     py_0    conda-forge
jpeg                      9b                   h024ee3a_2
json5                     0.9.0                      py_0    conda-forge
jsonschema                3.2.0            py37hc8dfbb8_1    conda-forge
jupyter                   1.0.0                      py_2    conda-forge
jupyter_client            6.1.2                      py_0    conda-forge
jupyter_console           6.1.0                      py_1    conda-forge
jupyter_core              4.6.3            py37hc8dfbb8_1    conda-forge
jupyterlab                2.0.1                      py_0    conda-forge
jupyterlab_server         1.0.7                      py_0    conda-forge
kiwisolver                1.1.0            py37h99015e2_1    conda-forge
krb5                      1.16.4               h173b8e3_0
ld_impl_linux-64          2.33.1               h53a641e_7
libboost                  1.67.0               h46d08c1_4
libcurl                   7.68.0               hda55be3_0    conda-forge
libedit                   3.1.20181209         hc058e9b_0
libffi                    3.2.1                hd88cf55_4
libgcc                    7.2.0                h69d50b8_2
libgcc-ng                 9.1.0                hdf63c60_0
libgfortran-ng            7.3.0                hdf63c60_0
libnetcdf                 4.7.3                hb80b6cc_0
libpng                    1.6.37               hbc83047_0
libsodium                 1.0.17               h516909a_0    conda-forge
libssh2                   1.8.2                h22169c7_2    conda-forge
libstdcxx-ng              9.1.0                hdf63c60_0
libtiff                   4.1.0                h2733197_0
libuuid                   1.0.3                h1bed415_2
libxcb                    1.13                 h1bed415_1
libxml2                   2.9.9                hea5a465_1
markupsafe                1.1.1            py37h8f50634_1    conda-forge
matplotlib                3.1.3                    py37_0
matplotlib-base           3.1.3            py37hef1b27d_0
mdanalysis                0.20.1           py37he1b5a44_0    conda-forge
mistune                   0.8.4           py37h516909a_1000    conda-forge
mkl                       2020.0                      166
mkl-service               2.3.0            py37he904b0f_0
mkl_fft                   1.0.15           py37ha843d7b_0
mkl_random                1.1.0            py37hd6b4f25_0
mmtf-python               1.1.2                      py_0    conda-forge
msgpack-python            1.0.0            py37h99015e2_1    conda-forge
nbconvert                 5.6.1                    py37_0    conda-forge
nbformat                  5.0.4                      py_0    conda-forge
ncurses                   6.2                  he6710b0_0
netcdf4                   1.5.3            py37hbf33ddf_0
networkx                  2.4                        py_0
nglview                   2.7.5              pyh5ca1d4c_0    conda-forge
notebook                  6.0.3                    py37_0    conda-forge
numpy                     1.18.1           py37h4f9e942_0
numpy-base                1.18.1           py37hde5b4d6_1
olefile                   0.46                     py37_0
openforcefield            0.6.0+163.g20712c1          pypi_0    pypi
openmm                    7.4.1           py37_cuda101_rc_1    omnia
openssl                   1.1.1f               h516909a_0    conda-forge
packaging                 20.3                       py_0
pandas                    1.0.3            py37h0573a6f_0
pandoc                    2.9.2                         0    conda-forge
pandocfilters             1.4.2                      py_1    conda-forge
parmed                    3.2.0+27.gaa15556a          pypi_0    pypi
parso                     0.6.2                      py_0    conda-forge
patsy                     0.5.1                      py_0    conda-forge
pcre                      8.43                 he6710b0_0
pexpect                   4.8.0            py37hc8dfbb8_1    conda-forge
pickleshare               0.7.5           py37hc8dfbb8_1001    conda-forge
pillow                    7.0.0            py37hb39fc2d_0
pip                       20.0.2                   py37_1
pixman                    0.38.0               h7b6447c_0
prometheus_client         0.7.1                      py_0    conda-forge
prompt-toolkit            3.0.5                      py_0    conda-forge
prompt_toolkit            3.0.5                         0    conda-forge
ptyprocess                0.6.0                   py_1001    conda-forge
py-boost                  1.67.0           py37h04863e7_4
py3dmol                   0.8.0                      py_0    conda-forge
pygments                  2.6.1                      py_0    conda-forge
pyparsing                 2.4.6                      py_0
pyqt                      5.9.2            py37hcca6a23_4    conda-forge
pyrsistent                0.16.0           py37h8f50634_0    conda-forge
python                    3.7.7           hcf32534_0_cpython
python-dateutil           2.8.1                      py_0
python_abi                3.7                     1_cp37m    conda-forge
pytz                      2019.3                     py_0
pyzmq                     19.0.0           py37hac76be4_1    conda-forge
qt                        5.9.7                h5867ecd_1
qtconsole                 4.7.2              pyh9f0ad1d_0    conda-forge
qtpy                      1.9.0                      py_0    conda-forge
rdkit                     2019.09.3.0      py37hc20afe1_1    rdkit
readline                  8.0                  h7b6447c_0
scikit-learn              0.22.1           py37hd81dba3_0
scipy                     1.4.1            py37h0b6359f_0
seaborn                   0.10.0                     py_1    conda-forge
send2trash                1.5.0                      py_0    conda-forge
setuptools                46.1.1                   py37_0
sip                       4.19.8           py37hf484d3e_0
six                       1.14.0                   py37_0
sqlite                    3.31.1               h7b6447c_0
statsmodels               0.11.1           py37h8f50634_1    conda-forge
terminado                 0.8.3            py37hc8dfbb8_1    conda-forge
testpath                  0.4.4                      py_0    conda-forge
tk                        8.6.8                hbc83047_0
tornado                   6.0.4            py37h8f50634_1    conda-forge
traitlets                 4.3.3            py37hc8dfbb8_1    conda-forge
wcwidth                   0.1.9              pyh9f0ad1d_0    conda-forge
webencodings              0.5.1                      py_1    conda-forge
werkzeug                  1.0.1              pyh9f0ad1d_0    conda-forge
wheel                     0.34.2                   py37_0
widgetsnbextension        3.5.1                    py37_0    conda-forge
xmltodict                 0.12.0                     py_0
xz                        5.2.4                h14c3975_4
zeromq                    4.3.2                he1b5a44_2    conda-forge
zipp                      3.1.0                      py_0    conda-forge
zlib                      1.2.11               h7b6447c_3
zstd                      1.3.7                h0b5b093_0
                                                                                                                                             
                                                                                                      

[mattwthompson]

Hmm, you're using a different version of AmberTools but I switched to the one you installed and still can't trigger this error. Nothing in your environment looks horribly out of date. If you update with conda install -c conda-forge ambertools does the issue persist? A conda update --all may also be helpful

[matteo-ambrosetti]

Ok, now I get a different error 👍 , this is in some way positive!

/home/matteo/anaconda3/envs/openmm/bin/to_be_dispatched/antechamber: Fatal Error!
Weird atomic valence (3) for atom (ID: 9, Name: C9).
       Possible open valence.
Traceback (most recent call last):
  File "error.py", line 25, in <module>
    system = forcefield.create_openmm_system(off_topology)
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/typing/engines/smirnoff/forcefield.py", line 1138, in create_openmm_system
    parameter_handler.create_force(system, topology, **kwargs)
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/typing/engines/smirnoff/parameters.py", line 2927, in create_force
    temp_mol.compute_partial_charges_am1bcc(toolkit_registry=toolkit_registry)
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/topology/molecule.py", line 2303, in compute_partial_charges_am1bcc
    self
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/utils/toolkits.py", line 3662, in call
    return method(*args, **kwargs)
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/site-packages/openforcefield-0.6.0+163.g20712c1-py3.7.egg/openforcefield/utils/toolkits.py", line 3191, in compute_partial_charges_am1bcc
    "charges.txt", "-pf", "yes"
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/subprocess.py", line 411, in check_output
    **kwargs).stdout
  File "/home/matteo/anaconda3/envs/openmm/lib/python3.7/subprocess.py", line 512, in run
    output=stdout, stderr=stderr)
subprocess.CalledProcessError: Command '['antechamber', '-i', 'charged.mol2', '-fi', 'mol2', '-o', 'charges2.mol2', '-fo', 'mol2', '-c', 'wc', '-cf', 'charges.txt', '-pf', 'yes']' returned non-zero exit status 1.

[j-wags]

Hi @matteo-ambrosetti,

The new error looks like the same issue as #532, which is caused by the new version of AmberTools adding a more strict input checker that doesn't like oxygen anions.

This will be fixed in our 0.7.0 release in a few weeks. Until then, you can apply an ugly patch to fix this:

• Get the location of toolkits.py:

python -c "from openforcefield.utils import toolkits; print(toolkits.__file__)"

• On line 2747, change

                    "yes -c bcc -nc {}".format(net_charge))

to

                    "yes -dr n -c bcc -nc {}".format(net_charge))

• On line 2754, change:

                    "-cf charges.txt -pf yes")

to

                    "-dr n -cf charges.txt -pf yes")

Apologies again for the ugly patch. We're going to get better about bugfix releases, we've just got a ton going on right now!

[matteo-ambrosetti]

Ok, now everything works perfectly.
Thanks again @j-wags!