REINVENT4: Dockstream failling to run due to SMILES parsing.

Hi,

I am currently recieving an error when trying to run with Dockstream. The program will run as expected for several cycles but it seems to be generating invalid smiles and passing these to docker which is causing an error. I have had to edit the SMILES strings in the error log for confidentiality.

Unfortunately I cannot share the structures.

At first I thought this was the issue:

The SMILES is opening and closing the rings in the wrong positions e.g. This SMILES “c1ccc2cccc2c1” - the correct SMILES - is being generated by REINVENT as “c1ccc1cccc1c1” but there seem to be multiple structures which cause no error and have this ‘issue’.

Second issue I see is the " at the start and end of the SMILES strings which are causing the two error messages when parsing and it fails to parse them.

I have also included the dockstream.log. dockstream.log

Any help debugging this issue would be much appreciated.

Many thanks, Alex

Loading dockstream/1.0.0
  Loading requirement: csd-enterprise/2023.2.1
Loading reinvent/4.0.35
  Loading requirement: python/3.10.13
Traceback (most recent call last):
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent_plugins/components/run_program.py", line 26, in run_command
    result = sp.run(command, **args)
  File "/progs/all/opensource/python/3.10.13/lib/python3.10/subprocess.py", line 526, in run
    raise CalledProcessError(retcode, process.args,
subprocess.CalledProcessError: Command '['/progs/all/opensource/dockstream/1.0.0/miniconda3/bin/python', '/progs/all/opensource/dockstream/1.0.0/source/docker.py', '-conf', './Gold_docking_for_reinvent.json', '-output_prefix', '16', '-smiles', '"#LIST_OF_SMILES#"', '-print_scores']' returned non-zero exit status 1.

During handling of the above exception, another exception occurred:

Traceback (most recent call last):
  File "/progs/all/opensource/reinvent/4.0.35/package/bin/reinvent", line 8, in <module>
    sys.exit(main())
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/Reinvent.py", line 292, in main
    runner(input_config, actual_device, tb_logdir, responder_config)
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/runmodes/RL/run_staged_learning.py", line 377, in run_staged_learning
    terminate = optimize(package.terminator)
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/runmodes/RL/learning.py", line 131, in optimize
    results = self.score()
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/runmodes/RL/learning.py", line 204, in score
    results = self.scoring_function(
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/scoring/scorer.py", line 105, in compute_results
    transform_result = compute_transform(
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/scoring/compute_scores.py", line 111, in compute_transform
    component_results = compute_component_scores(
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent/scoring/compute_scores.py", line 60, in compute_component_scores
    component_results = scoring_function(smilies_non_cached)
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent_plugins/components/comp_dockstream.py", line 75, in __call__
    result = run_command(command)
  File "/progs/all/opensource/reinvent/4.0.35/package/lib/python3.10/site-packages/reinvent_plugins/components/run_program.py", line 32, in run_command
    raise RuntimeError(
RuntimeError: reinvent_plugins.components.run_program: /progs/all/opensource/dockstream/1.0.0/miniconda3/bin/python /progs/all/opensource/dockstream/1.0.0/source/docker.py -conf ./Gold_docking_for_reinvent.json -output_prefix 16 -smiles "#LIST_OF_SMILES#" -print_scores has failed with exit code 1: stdout=, stderr=QStandardPaths: XDG_RUNTIME_DIR points to non-existing path '/run/user/16559', please create it with 0700 permissions.
[09:47:54] SMILES Parse Error: syntax error while parsing: "SMILES
[09:47:54] SMILES Parse Error: Failed parsing SMILES '"#SMILES' for input: '"#SMILES'
[09:47:54] SMILES Parse Error: syntax error while parsing: SMILES"
[09:47:54] SMILES Parse Error: Failed parsing SMILES '#SMILES"' for input: '#SMILES"'
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:54] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:55] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:55] Molecule does not have explicit Hs. Consider calling AddHs()
[09:47:55] Molecule does not have explicit Hs. Consider calling AddHs()
Traceback (most recent call last):
  File "/progs/all/opensource/dockstream/1.0.0/source/docker.py", line 175, in <module>
    docker.dock()
  File "/cluster/import/master/progs/all/opensource/dockstream/1.0.0/source/dockstream/core/docker.py", line 132, in dock
    self._dock(number_cores=number_cores)
  File "/cluster/import/master/progs/all/opensource/dockstream/1.0.0/source/dockstream/core/Gold/Gold_docker.py", line 216, in _dock
    cur_slice_sublists)
  File "/cluster/import/master/progs/all/opensource/dockstream/1.0.0/source/dockstream/core/Gold/Gold_docker.py", line 190, in _generate_temporary_input_output_files
    shutil.rmtree(cur_tmp_output_dir)
  File "/progs/all/opensource/dockstream/1.0.0/miniconda3/lib/python3.7/shutil.py", line 494, in rmtree
    _rmtree_safe_fd(fd, path, onerror)
  File "/progs/all/opensource/dockstream/1.0.0/miniconda3/lib/python3.7/shutil.py", line 413, in _rmtree_safe_fd
    onerror(os.scandir, path, sys.exc_info())
  File "/progs/all/opensource/dockstream/1.0.0/miniconda3/lib/python3.7/shutil.py", line 409, in _rmtree_safe_fd
    with os.scandir(topfd) as scandir_it:
OSError: [Errno 24] Too many open files: '/tmp/430137.1.gpu.q/tmpmpqdzfli'

The above exception was the direct cause of the following exception:

Traceback (most recent call last):
  File "/progs/all/opensource/dockstream/1.0.0/source/docker.py", line 187, in <module>
    raise DockingRunFailed() from e
dockstream.utils.dockstream_exceptions.DockingRunFailed