Error using ZINC Library

[Finn O.]

Hi,

I’m excited to use Autogrow, but after I got the PARP inhibitor example working, I tried to use my own configuration which fails but I’m not sure why. I’d like to use the provided 100 to 150 MW ZINC library with my own protein.
I’ll paste the JSON config file I’m using below:


{
"filename_of_receptor": "/home/ubuntu/EOHR.pdb",
"center_x": 34.457,
"center_y": 18.779,
"center_z": 108.487,
"size_x": 25.0,
"size_y": 25.0,
"size_z": 25.0,
"source_compound_file": "/home/ubuntu/100to150.smi",
"root_output_folder": "/home/ubuntu/EoHROut/",
"number_of_mutants_first_generation": 1000,
"number_of_crossovers_first_generation": 500,
"number_of_mutants": 200,
"number_of_crossovers": 100,
"number_elitism_advance_from_previous_gen": 20,
"top_mols_to_seed_next_generation": 100,
"diversity_mols_to_seed_first_generation": 30,
"diversity_seed_depreciation_per_gen": 2,
"num_generations": 20,
"conversion_choice": "ObabelConversion",
"obabel_path": "/usr/bin/obabel",
"mgltools_directory": "/home/ubuntu/mgltools_x86_64Linux2_1.5.6/",
"number_of_processors": -1,
"selector_choice": "Rank_Selector",
"max_variants_per_compound": 1,
"filter_source_compounds": false,
"use_docked_source_compounds": false,
"LipinskiLenientFilter": true,
"docking_exhaustiveness": 1,
"start_a_new_run": true,
"generate_plot": true,
"rescore_lig_efficiency": true,
"scoring_choice": "VINA",
"dock_choice": "QuickVina2Docking",
"gypsum_timeout_limit": 1,
"debug_mode": false,
"rxn_library": "all_rxns"
}

This results in a lot of warnings for poor formatting and for limiting variants, ~500 compounds are rejected. Then each thread fails and hangs. I’ve left it running for a few hours in this state and nothing further happens. The output is below. If you would like I can email you the full output.

Any help will be appreciated. Thanks.

Kind regards,

Finn


The Following ligands Failed to convert in Gypsum
Likely due to a Timeout
['Gen_1_Mutant_12_419030', 'Gen_1_Mutant_35_950717', 'Gen_1_Mutant_20_752731', 'Gen_1_Mutant_9_9291', 'Gen_1_Mutant_80_54668' ... another 500 entries here]
CONVERTING SMILES TO SDF COMPLETED
CONVERTING SDF TO PDB
Process Process-33:
Traceback (most recent call last):
File "/home/ubuntu/autogrow4/autogrow/operators/convert_files/conversion_to_3d.py", line 476, in convert_single_sdf_to_pdb
sdf_file_path, sanitize=True, removeHs=True, strictParsing=False
OSError: File error: Invalid input file /home/ubuntu/EoHROut/Run_0/generation_1/3D_SDFs/Gen_1_Mutant_51_694797__input1.sdf

During handling of the above exception, another exception occurred:

Traceback (most recent call last):
File "/home/ubuntu/anaconda3/lib/python3.7/multiprocessing/process.py", line 297, in _bootstrap
self.run()
File "/home/ubuntu/anaconda3/lib/python3.7/multiprocessing/process.py", line 99, in run
self._target(*self._args, **self._kwargs)
File "/home/ubuntu/autogrow4/autogrow/operators/convert_files/gypsum_dl/gypsum_dl/Parallelizer.py", line 666, in worker
result = func(*args)
File "/home/ubuntu/autogrow4/autogrow/operators/convert_files/conversion_to_3d.py", line 479, in convert_single_sdf_to_pdb
mols_no_hydrogen = [None for x in range(0, len(mols))]
TypeError: object of type 'NoneType' has no len()


[Jacob Durrant]

Hi Finn. Much thanks for your interest in AutoGrow4. I ran it by my resident AutoGrow4 expert, and he tells me that this bug was fixed in version 4.0.1: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/blob/4.0.1/CHANGELOG.md

Are you certain you’re using the latest version?

Also, he suggest that you consider adjusting a few parameters. The max_variants_per_compound, gypsum_timeout_limit, docking_exhaustiveness parameters are all very low (all set to 1). You might consider increasing them to the defaults or higher. Take care.

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