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OpenFreeEnergy
absolute hydration free energy calculation crash on methane
Describe the bug Hello! I have been trying to run an absolute hydration free energy calculation for methane. While the vacuum unit of the calculation concludes successfully, the solvent unit only manages to complete the plain molecular dynamics, then after it minimizes the alchemical system and starts equilibration, it crashes.
To Reproduce I'm creating a transformation json starting from the following sdf file, where methane is mobley_9055303:
mobley_9055303
-OEChem-01201715283D
5 4 0 0 0 0 0 0 0999 V2000
-0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.0570 1.0870 -0.0860 H 0 0 0 0 0 0 0 0 0 0 0 0
0.6200 -0.3970 -0.8070 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.0040 -0.4240 -0.0700 H 0 0 0 0 0 0 0 0 0 0 0 0
0.4420 -0.2670 0.9630 H 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0 0 0 0
1 3 1 0 0 0 0
1 4 1 0 0 0 0
1 5 1 0 0 0 0
M END
> <partial_charges>
-0.10869999975
0.0272000003606
0.0272000003606
0.0272000003606
0.0272000003606
> <partial_bond_orders>
1.0
1.0
1.0
1.0
> <atom_types>
c3
hc
hc
hc
hc
$$$$
The structure is read into the following script, where I generate a transformation json for each molecule present in the file:
def ahfe_simulation(input_file: str, durations) -> None:
import pathlib
from rdkit import Chem
from openfe import (
SmallMoleculeComponent,
SolventComponent,
ChemicalSystem,
Transformation,
)
from openfe.protocols.openmm_afe import AbsoluteSolvationProtocol
# read sdf files in for ligands
ligands_sdf = Chem.SDMolSupplier(input_file, removeHs=False)
ligand_mols = [SmallMoleculeComponent(sdf) for sdf in ligands_sdf]
# solvation
solvent = SolventComponent(positive_ion="K", negative_ion="Cl", neutralize=True)
# protocol - set simulations times and other settings
ahfe_settings = AbsoluteSolvationProtocol.default_settings()
(
ahfe_settings.solvent_simulation_settings.equilibration_length,
ahfe_settings.solvent_simulation_settings.production_length,
ahfe_settings.vacuum_simulation_settings.equilibration_length,
ahfe_settings.vacuum_simulation_settings.production_length,
) = durations
ahfe_settings.protocol_repeats = 1
ahfe_settings.solvent_equil_output_settings.output_indices = "all"
ahfe_settings.solvent_output_settings.output_indices = "all"
ahfe_settings.solvent_engine_settings.compute_platform = "cpu"
ahfe_settings.vacuum_engine_settings.compute_platform = "cpu"
ahfe_protocol = AbsoluteSolvationProtocol(settings=ahfe_settings)
transformation_dir = pathlib.Path("ahfe_json")
transformation_dir.mkdir(exist_ok=True)
for ligand in ligand_mols:
# chemical systems
system_a = ChemicalSystem(
{"ligand": ligand, "solvent": solvent}, name=ligand.name
)
system_b = ChemicalSystem({"solvent": solvent})
transformation = Transformation(
stateA=system_a,
stateB=system_b,
mapping=None,
protocol=ahfe_protocol,
name=f"{system_a.name}",
)
# use openfe CLI to run simulations and gather results
transformation.dump(transformation_dir / f"{transformation.name}.json")
if __name__ == "__main__":
from openff.units import unit
# ahfe simulation with default settings
# ahfe_durations = {
# "solvent": {"equilibration": 1, "production": 10},
# "vacuum": {"equilibration": 0.5, "production": 2},
# }
ahfe_durations = {
"solvent": {"equilibration": 1, "production": 10},
"vacuum": {"equilibration": 0.1, "production": 0.1},
}
ahfe_durations = (
ahfe_durations["solvent"]["equilibration"] * unit.nanosecond,
ahfe_durations["solvent"]["production"] * unit.nanosecond,
ahfe_durations["vacuum"]["equilibration"] * unit.nanosecond,
ahfe_durations["vacuum"]["production"] * unit.nanosecond,
)
ahfe_simulation("input_molecules.sdf", ahfe_durations)
Afterwards I run the calculation with openfe quickrun, and it fails once it reaches the alchemical simulations of the solvent unit.
Software versions
- Which operating system and version did you use? I am on NixOS 25.05
- Which method did you use to install this package? I'm running OpenFE from the 1.7.0 Docker image
- Copy/paste the output of
conda list(or the equivalent for your package manager): This is the output ofmicromamba listfrom within the container:
List of packages in environment: "/opt/conda"
Name Version Build Channel
───────────────────────────────────────────────────────────────────────────────────────────────
_openmp_mutex 4.5 5_kmp_llvm conda-forge
_python_abi3_support 1.0 hd8ed1ab_2 conda-forge
adjusttext 1.3.0 pyhd8ed1ab_0 conda-forge
adwaita-icon-theme 49.0 unix_0 conda-forge
ambertools 24.8 cuda_None_nompi_py312hbe1986e_101 conda-forge
annotated-types 0.7.0 pyhd8ed1ab_1 conda-forge
anyio 4.11.0 pyhcf101f3_0 conda-forge
argon2-cffi 25.1.0 pyhd8ed1ab_0 conda-forge
argon2-cffi-bindings 25.1.0 py312h4c3975b_1 conda-forge
arpack 3.9.1 nompi_hf03ea27_102 conda-forge
arrow 1.4.0 pyhcf101f3_0 conda-forge
asttokens 3.0.0 pyhd8ed1ab_1 conda-forge
async-lru 2.0.5 pyh29332c3_0 conda-forge
at-spi2-atk 2.38.0 h0630a04_3 conda-forge
at-spi2-core 2.40.3 h0630a04_0 conda-forge
atk-1.0 2.38.0 h04ea711_2 conda-forge
attrs 25.4.0 pyh71513ae_0 conda-forge
babel 2.17.0 pyhd8ed1ab_0 conda-forge
beautifulsoup4 4.14.2 pyha770c72_0 conda-forge
biopython 1.85 py312h4c3975b_2 conda-forge
bleach 6.2.0 pyh29332c3_4 conda-forge
bleach-with-css 6.2.0 h82add2a_4 conda-forge
blosc 1.21.6 he440d0b_1 conda-forge
brotli 1.1.0 hb03c661_4 conda-forge
brotli-bin 1.1.0 hb03c661_4 conda-forge
brotli-python 1.1.0 py312h1289d80_4 conda-forge
bson 0.5.10 pyhd8ed1ab_0 conda-forge
bzip2 1.0.8 hda65f42_8 conda-forge
c-ares 1.34.5 hb9d3cd8_0 conda-forge
c-blosc2 2.21.3 h4cfbee9_0 conda-forge
ca-certificates 2025.10.5 hbd8a1cb_0 conda-forge
cached-property 1.5.2 hd8ed1ab_1 conda-forge
cached_property 1.5.2 pyha770c72_1 conda-forge
cachetools 6.2.1 pyhd8ed1ab_0 conda-forge
cairo 1.18.4 h3394656_0 conda-forge
certifi 2025.10.5 pyhd8ed1ab_0 conda-forge
cffi 2.0.0 py312h35888ee_0 conda-forge
cftime 1.6.4 py312h4f23490_2 conda-forge
charset-normalizer 3.4.4 pyhd8ed1ab_0 conda-forge
cinnabar 0.5.0 pyhd8ed1ab_0 conda-forge
click 8.3.0 pyh707e725_0 conda-forge
click-option-group 0.5.6 pyhd8ed1ab_0 conda-forge
colorama 0.4.6 pyhd8ed1ab_1 conda-forge
comm 0.2.3 pyhe01879c_0 conda-forge
contourpy 1.3.3 py312hd9148b4_2 conda-forge
cpython 3.12.12 py312hd8ed1ab_1 conda-forge
cudatoolkit 11.7.0 hd8887f6_11 conda-forge
cycler 0.12.1 pyhd8ed1ab_1 conda-forge
cyrus-sasl 2.1.28 hd9c7081_0 conda-forge
dbus 1.16.2 h3c4dab8_0 conda-forge
debugpy 1.8.17 py312h8285ef7_0 conda-forge
decorator 5.2.1 pyhd8ed1ab_0 conda-forge
defusedxml 0.7.1 pyhd8ed1ab_0 conda-forge
dill 0.4.0 pyhd8ed1ab_0 conda-forge
epoxy 1.5.10 hb03c661_2 conda-forge
exceptiongroup 1.3.0 pyhd8ed1ab_0 conda-forge
execnet 2.1.1 pyhd8ed1ab_1 conda-forge
executing 2.2.1 pyhd8ed1ab_0 conda-forge
fftw 3.3.10 nompi_hf1063bd_110 conda-forge
filelock 3.20.0 pyhd8ed1ab_0 conda-forge
flexcache 0.3 pyhd8ed1ab_1 conda-forge
flexparser 0.4 pyhd8ed1ab_1 conda-forge
font-ttf-dejavu-sans-mono 2.37 hab24e00_0 conda-forge
font-ttf-inconsolata 3.000 h77eed37_0 conda-forge
font-ttf-source-code-pro 2.038 h77eed37_0 conda-forge
font-ttf-ubuntu 0.83 h77eed37_3 conda-forge
fontconfig 2.15.0 h7e30c49_1 conda-forge
fonts-conda-ecosystem 1 0 conda-forge
fonts-conda-forge 1 0 conda-forge
fonttools 4.60.1 py312h8a5da7c_0 conda-forge
fqdn 1.5.1 pyhd8ed1ab_1 conda-forge
freetype 2.14.1 ha770c72_0 conda-forge
freetype-py 2.3.0 pyhd8ed1ab_0 conda-forge
fribidi 1.0.16 hb03c661_0 conda-forge
fsspec 2025.9.0 pyhd8ed1ab_0 conda-forge
gdk-pixbuf 2.44.4 h2b0a6b4_0 conda-forge
git 2.51.1 pl5321h8305f47_0 conda-forge
glib-tools 2.86.0 hf516916_0 conda-forge
gmp 6.3.0 hac33072_2 conda-forge
gmpy2 2.2.1 py312hcaba1f9_1 conda-forge
graphite2 1.3.14 hecca717_2 conda-forge
graphviz 13.1.2 h87b6fe6_0 conda-forge
greenlet 3.2.4 py312h1289d80_1 conda-forge
griddataformats 1.0.2 pyhd8ed1ab_1 conda-forge
gsd 4.2.0 h31e983c_0 conda-forge
gtk3 3.24.43 h021d004_4 conda-forge
gts 0.7.6 h977cf35_4 conda-forge
gufe 1.7.0 pyhd8ed1ab_0 conda-forge
h11 0.16.0 pyhd8ed1ab_0 conda-forge
h2 4.3.0 pyhcf101f3_0 conda-forge
h5py 3.15.1 nompi_py312ha4f8f14_100 conda-forge
harfbuzz 12.1.0 h15599e2_0 conda-forge
hdf4 4.2.15 h2a13503_7 conda-forge
hdf5 1.14.6 nompi_h6e4c0c1_103 conda-forge
hicolor-icon-theme 0.17 ha770c72_2 conda-forge
hpack 4.1.0 pyhd8ed1ab_0 conda-forge
httpcore 1.0.9 pyh29332c3_0 conda-forge
httpx 0.28.1 pyhd8ed1ab_0 conda-forge
hyperframe 6.1.0 pyhd8ed1ab_0 conda-forge
icu 75.1 he02047a_0 conda-forge
idna 3.11 pyhd8ed1ab_0 conda-forge
importlib-metadata 8.7.0 pyhe01879c_1 conda-forge
importlib_resources 6.5.2 pyhd8ed1ab_0 conda-forge
iniconfig 2.3.0 pyhd8ed1ab_0 conda-forge
ipycytoscape 1.3.3 pyhd8ed1ab_1 conda-forge
ipykernel 7.0.1 pyha191276_0 conda-forge
ipython 9.6.0 pyhfa0c392_0 conda-forge
ipython_pygments_lexers 1.1.1 pyhd8ed1ab_0 conda-forge
ipywidgets 8.1.7 pyhd8ed1ab_0 conda-forge
isoduration 20.11.0 pyhd8ed1ab_1 conda-forge
jax 0.7.0 pyhd8ed1ab_0 conda-forge
jaxlib 0.7.0 cpu_py312h73730d4_1 conda-forge
jedi 0.19.2 pyhd8ed1ab_1 conda-forge
jinja2 3.1.6 pyhd8ed1ab_0 conda-forge
joblib 1.5.2 pyhd8ed1ab_0 conda-forge
jq 1.8.1 h73b1eb8_0 conda-forge
json5 0.12.1 pyhd8ed1ab_0 conda-forge
jsonpointer 3.0.0 py312h7900ff3_2 conda-forge
jsonschema 4.25.1 pyhe01879c_0 conda-forge
jsonschema-specifications 2025.9.1 pyhcf101f3_0 conda-forge
jsonschema-with-format-nongpl 4.25.1 he01879c_0 conda-forge
jupyter-lsp 2.3.0 pyhcf101f3_0 conda-forge
jupyter_client 8.6.3 pyhd8ed1ab_1 conda-forge
jupyter_core 5.9.1 pyhc90fa1f_0 conda-forge
jupyter_events 0.12.0 pyh29332c3_0 conda-forge
jupyter_server 2.17.0 pyhcf101f3_0 conda-forge
jupyter_server_terminals 0.5.3 pyhd8ed1ab_1 conda-forge
jupyterlab 4.4.10 pyhd8ed1ab_0 conda-forge
jupyterlab_pygments 0.3.0 pyhd8ed1ab_2 conda-forge
jupyterlab_server 2.28.0 pyhcf101f3_0 conda-forge
jupyterlab_widgets 3.0.15 pyhd8ed1ab_0 conda-forge
kartograf 1.2.0 pyhd8ed1ab_0 conda-forge
keyutils 1.6.3 hb9d3cd8_0 conda-forge
kiwisolver 1.4.9 py312h0a2e395_1 conda-forge
konnektor 0.2.0 pyhe01879c_0 conda-forge
krb5 1.21.3 h659f571_0 conda-forge
lark 1.3.0 pyhd8ed1ab_0 conda-forge
lcms2 2.17 h717163a_0 conda-forge
ld_impl_linux-64 2.44 ha97dd6f_2 conda-forge
lerc 4.0.0 h0aef613_1 conda-forge
libabseil 20250127.1 cxx17_hbbce691_0 conda-forge
libaec 1.1.4 h3f801dc_0 conda-forge
libblas 3.9.0 37_h5875eb1_mkl conda-forge
libboost 1.86.0 hed09d94_4 conda-forge
libboost-python 1.86.0 py312hf890105_4 conda-forge
libbrotlicommon 1.1.0 hb03c661_4 conda-forge
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libcblas 3.9.0 37_hfef963f_mkl conda-forge
libcups 2.3.3 hb8b1518_5 conda-forge
libcurl 8.16.0 h4e3cde8_0 conda-forge
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libdrm 2.4.125 hb03c661_1 conda-forge
libedit 3.1.20250104 pl5321h7949ede_0 conda-forge
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libegl-devel 1.7.0 ha4b6fd6_2 conda-forge
libev 4.33 hd590300_2 conda-forge
libexpat 2.7.1 hecca717_0 conda-forge
libffi 3.4.6 h2dba641_1 conda-forge
libfreetype 2.14.1 ha770c72_0 conda-forge
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libgcc 15.2.0 h767d61c_7 conda-forge
libgcc-ng 15.2.0 h69a702a_7 conda-forge
libgd 2.3.3 h6f5c62b_11 conda-forge
libgfortran 15.2.0 h69a702a_7 conda-forge
libgfortran-ng 15.2.0 h69a702a_7 conda-forge
libgfortran5 15.2.0 hcd61629_7 conda-forge
libgl 1.7.0 ha4b6fd6_2 conda-forge
libgl-devel 1.7.0 ha4b6fd6_2 conda-forge
libglib 2.86.0 h1fed272_0 conda-forge
libglvnd 1.7.0 ha4b6fd6_2 conda-forge
libglx 1.7.0 ha4b6fd6_2 conda-forge
libglx-devel 1.7.0 ha4b6fd6_2 conda-forge
libgomp 15.2.0 h767d61c_7 conda-forge
libgrpc 1.71.0 h8e591d7_1 conda-forge
libhwloc 2.12.1 default_h3d81e11_1000 conda-forge
libiconv 1.18 h3b78370_2 conda-forge
libjpeg-turbo 3.1.0 hb9d3cd8_0 conda-forge
liblapack 3.9.0 37_h5e43f62_mkl conda-forge
liblzma 5.8.1 hb9d3cd8_2 conda-forge
libnetcdf 4.9.2 nompi_h21f7587_118 conda-forge
libnghttp2 1.67.0 had1ee68_0 conda-forge
libnsl 2.0.1 hb9d3cd8_1 conda-forge
libntlm 1.8 hb9d3cd8_0 conda-forge
libpciaccess 0.18 hb9d3cd8_0 conda-forge
libpng 1.6.50 h421ea60_1 conda-forge
libpq 18.0 h3675c94_0 conda-forge
libprotobuf 5.29.3 h7460b1f_2 conda-forge
librdkit 2025.09.1 h3c5c181_1 conda-forge
libre2-11 2025.06.26 hba17884_0 conda-forge
librsvg 2.58.4 h49af25d_2 conda-forge
libsodium 1.0.20 h4ab18f5_0 conda-forge
libsqlite 3.50.4 h0c1763c_0 conda-forge
libssh2 1.11.1 hcf80075_0 conda-forge
libstdcxx 15.2.0 h8f9b012_7 conda-forge
libstdcxx-ng 15.2.0 h4852527_7 conda-forge
libtiff 4.7.1 h8261f1e_0 conda-forge
libtorch 2.6.0 cpu_mkl_hec71012_102 conda-forge
libuuid 2.41.2 he9a06e4_0 conda-forge
libuv 1.51.0 hb03c661_1 conda-forge
libwebp-base 1.6.0 hd42ef1d_0 conda-forge
libxcb 1.17.0 h8a09558_0 conda-forge
libxcrypt 4.4.36 hd590300_1 conda-forge
libxkbcommon 1.11.0 he8b52b9_0 conda-forge
libxml2 2.13.8 h04c0eec_1 conda-forge
libxslt 1.1.43 h7a3aeb2_0 conda-forge
libzip 1.11.2 h6991a6a_0 conda-forge
libzlib 1.3.1 hb9d3cd8_2 conda-forge
lightning-utilities 0.15.2 pyhd8ed1ab_0 conda-forge
llvm-openmp 21.1.4 h4922eb0_0 conda-forge
llvmlite 0.45.1 py312h7424e68_0 conda-forge
lomap2 3.2.1 pyhd8ed1ab_3 conda-forge
lxml 6.0.2 py312h70dad80_0 conda-forge
lz4-c 1.10.0 h5888daf_1 conda-forge
markdown-it-py 4.0.0 pyhd8ed1ab_0 conda-forge
markupsafe 3.0.3 py312h8a5da7c_0 conda-forge
matplotlib-base 3.10.7 py312he3d6523_0 conda-forge
matplotlib-inline 0.2.1 pyhd8ed1ab_0 conda-forge
mda-xdrlib 0.2.0 pyhd8ed1ab_1 conda-forge
mdanalysis 2.10.0 py312hf79963d_1 conda-forge
mdtraj 1.11.0 np2py312h8baca0b_3 conda-forge
mdurl 0.1.2 pyhd8ed1ab_1 conda-forge
mistune 3.1.4 pyhcf101f3_0 conda-forge
mkl 2024.2.2 ha770c72_17 conda-forge
ml_dtypes 0.5.1 py312hf79963d_1 conda-forge
mmtf-python 1.1.3 pyhd8ed1ab_0 conda-forge
mpc 1.3.1 h24ddda3_1 conda-forge
mpfr 4.2.1 h90cbb55_3 conda-forge
mpiplus v0.0.2 pyhd8ed1ab_0 conda-forge
mpmath 1.3.0 pyhd8ed1ab_1 conda-forge
mrcfile 1.5.4 pyhd8ed1ab_0 conda-forge
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munkres 1.1.4 pyhd8ed1ab_1 conda-forge
narwhals 2.9.0 pyhcf101f3_0 conda-forge
nbclient 0.10.2 pyhd8ed1ab_0 conda-forge
nbconvert-core 7.16.6 pyhcf101f3_1 conda-forge
nbformat 5.10.4 pyhd8ed1ab_1 conda-forge
ncurses 6.5 h2d0b736_3 conda-forge
nest-asyncio 1.6.0 pyhd8ed1ab_1 conda-forge
netcdf-fortran 4.6.2 nompi_h5aa5643_101 conda-forge
netcdf4 1.7.2 nompi_py312hdd76c12_103 conda-forge
networkx 3.5 pyhe01879c_0 conda-forge
notebook 7.4.7 pyhd8ed1ab_0 conda-forge
notebook-shim 0.2.4 pyhd8ed1ab_1 conda-forge
numba 0.62.1 py312h907b442_0 conda-forge
numexpr 2.14.1 mkl_py312hf8315b2_0 conda-forge
numpy 1.26.4 py312heda63a1_0 conda-forge
ocl-icd 2.3.3 hb9d3cd8_0 conda-forge
ocl-icd-system 1.0.0 1 conda-forge
oniguruma 6.9.10 hb9d3cd8_0 conda-forge
opencl-headers 2025.06.13 h5888daf_0 conda-forge
openfe 1.7.0 pyhd8ed1ab_0 conda-forge
openfe-analysis 0.3.1 pyhd8ed1ab_0 conda-forge
openfe-base 1.7.0 pyhd8ed1ab_0 conda-forge
openff-amber-ff-ports 2025.09.0 pyhd8ed1ab_0 conda-forge
openff-forcefields 2025.10.1 pyhd8ed1ab_0 conda-forge
openff-interchange 0.4.8 pyhd8ed1ab_1 conda-forge
openff-interchange-base 0.4.8 pyhd8ed1ab_1 conda-forge
openff-nagl 0.5.4 pyhd8ed1ab_0 conda-forge
openff-nagl-base 0.5.4 pyhd8ed1ab_0 conda-forge
openff-nagl-models 2025.9.0 pyhd8ed1ab_0 conda-forge
openff-toolkit 0.17.1 pyhd8ed1ab_0 conda-forge
openff-toolkit-base 0.17.1 pyhd8ed1ab_0 conda-forge
openff-units 0.3.1 pyhd8ed1ab_2 conda-forge
openff-utilities 0.1.16 pyhd8ed1ab_0 conda-forge
openjpeg 2.5.4 h55fea9a_0 conda-forge
openldap 2.6.10 he970967_0 conda-forge
openmm 8.1.1 py312hce710af_1 conda-forge
openmmforcefields 0.14.2 pyhd8ed1ab_0 conda-forge
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openssl 3.5.4 h26f9b46_0 conda-forge
opt_einsum 3.4.0 pyhd8ed1ab_1 conda-forge
optree 0.17.0 py312hd9148b4_1 conda-forge
overrides 7.7.0 pyhd8ed1ab_1 conda-forge
packaging 25.0 pyh29332c3_1 conda-forge
pandas 2.3.3 py312hf79963d_1 conda-forge
pandocfilters 1.5.0 pyhd8ed1ab_0 conda-forge
pango 1.56.4 hadf4263_0 conda-forge
parmed 4.3.0 py312ha9124a0_2 conda-forge
parso 0.8.5 pyhcf101f3_0 conda-forge
patsy 1.0.2 pyhcf101f3_0 conda-forge
pcre2 10.46 h1321c63_0 conda-forge
pdbfixer 1.9 pyh1a96a4e_0 conda-forge
perl 5.32.1 7_hd590300_perl5 conda-forge
pexpect 4.9.0 pyhd8ed1ab_1 conda-forge
pickleshare 0.7.5 pyhd8ed1ab_1004 conda-forge
pillow 11.3.0 py312h7b42cdd_3 conda-forge
pint 0.24.4 pyhe01879c_2 conda-forge
pip 25.2 pyh8b19718_0 conda-forge
pixman 0.46.4 h54a6638_1 conda-forge
platformdirs 4.5.0 pyhcf101f3_0 conda-forge
plotly 6.3.1 pyhd8ed1ab_0 conda-forge
plugcli 0.2.1 pyhd8ed1ab_0 conda-forge
pluggy 1.6.0 pyhd8ed1ab_0 conda-forge
pooch 1.8.2 pyhd8ed1ab_3 conda-forge
prometheus_client 0.23.1 pyhd8ed1ab_0 conda-forge
prompt-toolkit 3.0.52 pyha770c72_0 conda-forge
psutil 7.1.1 py312h4c3975b_0 conda-forge
pthread-stubs 0.4 hb9d3cd8_1002 conda-forge
ptyprocess 0.7.0 pyhd8ed1ab_1 conda-forge
pure_eval 0.2.3 pyhd8ed1ab_1 conda-forge
py-cpuinfo 9.0.0 pyhd8ed1ab_1 conda-forge
py3dmol 2.5.3 pyhd8ed1ab_0 conda-forge
pybind11 3.0.1 pyh7a1b43c_0 conda-forge
pybind11-global 3.0.1 pyhc7ab6ef_0 conda-forge
pycairo 1.28.0 py312h2596900_1 conda-forge
pycparser 2.22 pyh29332c3_1 conda-forge
pydantic 2.11.10 pyh3cfb1c2_0 conda-forge
pydantic-core 2.33.2 py312h680f630_0 conda-forge
pyedr 0.8.0 pyhd8ed1ab_1 conda-forge
pygments 2.19.2 pyhd8ed1ab_0 conda-forge
pygraphviz 1.14 py312hdfa1987_2 conda-forge
pymbar 4.2.0 h7900ff3_1 conda-forge
pymbar-core 4.2.0 py312h4f23490_1 conda-forge
pyparsing 3.2.5 pyhcf101f3_0 conda-forge
pysocks 1.7.1 pyha55dd90_7 conda-forge
pytables 3.10.2 py312hefc0c3f_9 conda-forge
pytest 8.4.2 pyhd8ed1ab_0 conda-forge
pytest-datadir 1.8.0 pyhd8ed1ab_0 conda-forge
pytest-regressions 2.8.3 pyhc455866_0 conda-forge
pytest-xdist 3.8.0 pyhd8ed1ab_0 conda-forge
python 3.12.12 hfe2f287_0_cpython conda-forge
python-constraint 1.4.0 pyhff2d567_1 conda-forge
python-dateutil 2.9.0.post0 pyhe01879c_2 conda-forge
python-fastjsonschema 2.21.2 pyhe01879c_0 conda-forge
python-gil 3.12.12 hd8ed1ab_1 conda-forge
python-json-logger 2.0.7 pyhd8ed1ab_0 conda-forge
python-tzdata 2025.2 pyhd8ed1ab_0 conda-forge
python_abi 3.12 8_cp312 conda-forge
pytng 0.3.4 py312heed6b8f_0 conda-forge
pytorch 2.6.0 cpu_mkl_py312_he110f90_102 conda-forge
pytorch-lightning 2.5.5 pyh2a12c56_0 conda-forge
pytz 2025.2 pyhd8ed1ab_0 conda-forge
pyyaml 6.0.3 py312h8a5da7c_0 conda-forge
pyzmq 27.1.0 py312hfb55c3c_0 conda-forge
qhull 2020.2 h434a139_5 conda-forge
rdkit 2025.09.1 py312h3ecb6ed_1 conda-forge
re2 2025.06.26 h9925aae_0 conda-forge
readline 8.2 h8c095d6_2 conda-forge
referencing 0.37.0 pyhcf101f3_0 conda-forge
reportlab 4.4.4 py312h4c3975b_0 conda-forge
requests 2.32.5 pyhd8ed1ab_0 conda-forge
rfc3339-validator 0.1.4 pyhd8ed1ab_1 conda-forge
rfc3986-validator 0.1.1 pyh9f0ad1d_0 conda-forge
rfc3987-syntax 1.1.0 pyhe01879c_1 conda-forge
rich 14.2.0 pyhcf101f3_0 conda-forge
rlpycairo 0.4.0 pyh6c17108_0 conda-forge
rpds-py 0.28.0 py312h868fb18_1 conda-forge
scikit-learn 1.7.2 py312h4f0b9e3_0 conda-forge
scikit-mol 0.6.1 pyhd8ed1ab_0 conda-forge
scipy 1.16.2 py312h7a1785b_0 conda-forge
seaborn 0.13.2 hd8ed1ab_3 conda-forge
seaborn-base 0.13.2 pyhd8ed1ab_3 conda-forge
send2trash 1.8.3 pyh0d859eb_1 conda-forge
setuptools 80.9.0 pyhff2d567_0 conda-forge
six 1.17.0 pyhe01879c_1 conda-forge
sleef 3.9.0 ha0421bc_0 conda-forge
snappy 1.2.2 h03e3b7b_0 conda-forge
sniffio 1.3.1 pyhd8ed1ab_1 conda-forge
soupsieve 2.8 pyhd8ed1ab_0 conda-forge
spectate 1.0.1 pyhd8ed1ab_0 conda-forge
sqlalchemy 2.0.44 py312h4c3975b_0 conda-forge
stack_data 0.6.3 pyhd8ed1ab_1 conda-forge
statsmodels 0.14.5 py312h4f23490_1 conda-forge
sympy 1.14.0 pyh2585a3b_105 conda-forge
tbb 2021.13.0 hb60516a_3 conda-forge
terminado 0.18.1 pyh0d859eb_0 conda-forge
threadpoolctl 3.6.0 pyhecae5ae_0 conda-forge
tidynamics 1.1.2 pyhd8ed1ab_0 conda-forge
tinycss2 1.4.0 pyhd8ed1ab_0 conda-forge
tinydb 4.8.2 pyhd8ed1ab_1 conda-forge
tk 8.6.13 noxft_hd72426e_102 conda-forge
tomli 2.3.0 pyhcf101f3_0 conda-forge
torchmetrics 1.8.2 pyhd8ed1ab_0 conda-forge
tornado 6.5.2 py312h4c3975b_1 conda-forge
tqdm 4.67.1 pyhd8ed1ab_1 conda-forge
traitlets 5.14.3 pyhd8ed1ab_1 conda-forge
typing-extensions 4.15.0 h396c80c_0 conda-forge
typing-inspection 0.4.2 pyhd8ed1ab_0 conda-forge
typing_extensions 4.15.0 pyhcf101f3_0 conda-forge
typing_utils 0.1.0 pyhd8ed1ab_1 conda-forge
tzdata 2025b h78e105d_0 conda-forge
unicodedata2 16.0.0 py312h4c3975b_1 conda-forge
uri-template 1.3.0 pyhd8ed1ab_1 conda-forge
urllib3 2.5.0 pyhd8ed1ab_0 conda-forge
validators 0.35.0 pyhd8ed1ab_0 conda-forge
wayland 1.24.0 h3e06ad9_0 conda-forge
wcwidth 0.2.14 pyhd8ed1ab_0 conda-forge
webcolors 24.11.1 pyhd8ed1ab_0 conda-forge
webencodings 0.5.1 pyhd8ed1ab_3 conda-forge
websocket-client 1.9.0 pyhd8ed1ab_0 conda-forge
wheel 0.45.1 pyhd8ed1ab_1 conda-forge
widgetsnbextension 4.0.14 pyhd8ed1ab_0 conda-forge
xkeyboard-config 2.46 hb03c661_0 conda-forge
xmltodict 1.0.2 pyhcf101f3_0 conda-forge
xorg-libice 1.1.2 hb9d3cd8_0 conda-forge
xorg-libsm 1.2.6 he73a12e_0 conda-forge
xorg-libx11 1.8.12 h4f16b4b_0 conda-forge
xorg-libxau 1.0.12 hb9d3cd8_0 conda-forge
xorg-libxcomposite 0.4.6 hb9d3cd8_2 conda-forge
xorg-libxcursor 1.2.3 hb9d3cd8_0 conda-forge
xorg-libxdamage 1.1.6 hb9d3cd8_0 conda-forge
xorg-libxdmcp 1.1.5 hb9d3cd8_0 conda-forge
xorg-libxext 1.3.6 hb9d3cd8_0 conda-forge
xorg-libxfixes 6.0.2 hb03c661_0 conda-forge
xorg-libxi 1.8.2 hb9d3cd8_0 conda-forge
xorg-libxinerama 1.1.5 h5888daf_1 conda-forge
xorg-libxrandr 1.5.4 hb9d3cd8_0 conda-forge
xorg-libxrender 0.9.12 hb9d3cd8_0 conda-forge
xorg-libxt 1.3.1 hb9d3cd8_0 conda-forge
xorg-libxtst 1.2.5 hb9d3cd8_3 conda-forge
xorg-libxxf86vm 1.1.6 hb9d3cd8_0 conda-forge
xorg-xorgproto 2024.1 hb9d3cd8_1 conda-forge
yaml 0.2.5 h280c20c_3 conda-forge
zeromq 4.3.5 h387f397_9 conda-forge
zipp 3.23.0 pyhd8ed1ab_0 conda-forge
zlib 1.3.1 hb9d3cd8_2 conda-forge
zlib-ng 2.2.5 hde8ca8f_0 conda-forge
zstandard 0.25.0 py312h5253ce2_0 conda-forge
zstd 1.5.7 hb8e6e7a_2 conda-forge
Output
INFO:openmmtools.multistate.multistatesampler:Equilibration iteration 1/400
WARNING:py.warnings:/opt/conda/lib/python3.12/site-packages/openmmtools/mcmc.py:723: UserWarning: Particle coordinate is NaN. For more information, see https://github.com/openmm/openmm/wiki/Frequently-Asked-Questions#nan
warnings.warn(str(e))
WARNING:openmmtools.mcmc:Potential energy is NaN after 0 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 1 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 2 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 3 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 4 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 5 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 6 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 7 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 8 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 9 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 10 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 11 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 12 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 13 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 14 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 15 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 16 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 17 attempts of integration with move LangevinDynamicsMove Attempting a restart...
WARNING:openmmtools.mcmc:Potential energy is NaN after 18 attempts of integration with move LangevinDynamicsMove Attempting a restart...
ERROR:openmmtools.mcmc:Potential energy is NaN after 19 attempts of integration with move LangevinDynamicsMove Trying to reinitialize Context as a last-resort restart attempt...
ERROR:openmmtools.mcmc:Potential energy is NaN after 20 attempts of integration with move LangevinDynamicsMove
CRITICAL:openmmtools.multistate.multistatesampler:Propagating replica 0 at state 0 resulted in a NaN!
The state of the system and integrator before the error were saved in /home/openfe/openfe_issue/ahfe_json/shared_AbsoluteSolvationSolventUnit-cbd14d92394746debeae61fa9808d276_attempt_2/nan-error-logs
Expected behavior I expected the simulation to conclude successfully.
Additional context I've tried running the simulation with different methane input files to no avail. I've also tested the 1.5.0 Docker image. When I print the last saved state to PDB with OpenMM there does not seem to be anything out of place. Running this on the HPC system that will run the calculations for multiple molecules, the same error occurs. I am wilfully running the calculation on CPU because that is what will be available on the node. I have made multiple attempts, but the solvent leg always fails.
Thank you in advance for your help!
Thanks for the report @Lumber1432
I think I've seen a similar problem lately but I'm only now realising it's maybe a real bug.
Could you try running using only a few CPU cores? Try something like export OPENMM_CPU_THREADS=2.
Hello @IAlibay, thank you for your prompt response. I have tried running the simulation within a container with OPENMM_CPU_THREADS=2 set, but it still crashed with the same error.
I am not sure if this is relevant, but since you mentioned modifying the core count I thought I would mention; when running this simulation on the compute node of the HPC system, I get some strange behavior. No matter how I try to get the process to use all cores available on the node, the process only ever uses a few (2, maybe 3 cores) to run the simulation. The only way I have been able to circumvent this has been by creating the SolvenUnit manually and running it separately. The process then uses all cores available. I have not tested, but assume the same would happen with the VacuumUnit. I was wondering if this is intended behavior.
Thank you again and let me know if there is anything else I can do.
I am not sure if this is relevant, but since you mentioned modifying the core count I thought I would mention; when running this simulation on the compute node of the HPC system, I get some strange behavior. No matter how I try to get the process to use all cores available on the node, the process only ever uses a few (2, maybe 3 cores) to run the simulation. The only way I have been able to circumvent this has been by creating the SolvenUnit manually and running it separately. The process then uses all cores available. I have not tested, but assume the same would happen with the VacuumUnit. I was wondering if this is intended behavior.
Ah thanks so much for reporting this, I just looked into the code and this is a separate (but equally legitimate) bug! I'll open a separate issue.
Regarding the methane simulation failure you present, that is rather interesting. I'll try to replicate it on my end.
@Lumber1432 I have been able to reproduce this locally - it looks like for > 1 CPU threads, the system crashes (it works fine on GPUs).
I'm not sure exactly what's going on here, I wonder if it's because the system is too small to decompose in a sensible way. By any chance, have you seen similar issues with larger ligands?
@IAlibay I tried to run the same simulation for toluene once to test whether that system would crash too, and it did. However, I did not test that molecule as extensively as I did methane. I haven't tried anything larger.
@IAlibay I am facing same issue lately when processing a ternary complex. I am wondering if this issue is specific to the simulation setup or when would this issue be triggered?
@ziyueyang37 - this should only be happening during simulation execution, rather than setup. Could you provide more information about what failure you are seeing?
@IAlibay, thanks for replying. This is the error message in the output json file for 'complex' system : raise SimulationNaNError(message)\nopenmmtools.multistate.utils.SimulationNaNError: Propagating replica 0 at state 0 resulted in a NaN!\nThe state of the system and integrator before the error were saved in ****
The 'solvent' system did not raise error.
Thanks for the info @ziyueyang37 ! That does look like you're also getting a failure at simulation run time. Although since you're saying you are getting an issue with the complex (I assume this is an RBFE simulation?), I wonder if that might be a separate problem, e.g. bad initial configuration. Could you maybe open a separate issue with more details?
Regarding the CPU simulation failure for AHFEs, I can't seem to be able to reproduce them with RHFEs or plain MD. I'm not sure exactly what is happening there. We are going to keep looking at it, but I'm afraid it might take a while to understand what is happening.