Trying Gypsum in autogrow4

[Bharti]

Hi,
All your tools are just fantastic and the algorithm is really though through.
However, I have been trying to work with Autogrow 4 on my source compounds fragmented by using the script provided in the program.
After running 2 generations successfully, the program halted at generation 3 with the following message…
Kindly guide if the gypsum timeout parameter need to be adjusted or what might be the problem as last two generations were looking pretty good.

The Following ligands Failed to convert in Gypsum
Likely due to a Timeout
[‘Gen_3_Mutant_85_519998’, ‘Gen_3_Cross_907363’, ‘Gen_3_Mutant_80_854419’, ‘Gen_3_Mutant_46_973078’, ‘Gen_3_Mutant_51_310184’, ‘Gen_3_Mutant_19_511583’, ‘Gen_3_Mutant_18_754618’, ‘Gen_3_Mutant_80_710944’, ‘Gen_3_Mutant_80_41323’, ‘Gen_3_Mutant_12_457340’, ‘Gen_3_Mutant_47_733063’, ‘Gen_3_Mutant_89_62206’, ‘Gen_3_Mutant_87_80064’, ‘Gen_3_Mutant_51_33050’, ‘Gen_3_Mutant_85_486207’, ‘Gen_3_Cross_441667’, ‘Gen_3_Cross_302726’, ‘Gen_3_Mutant_80_853242’, ‘Gen_3_Mutant_87_201239’, ‘Gen_3_Mutant_51_35905’, ‘Gen_3_Mutant_6_878484’, ‘Gen_3_Cross_810826’, ‘Gen_3_Cross_499536’, ‘Gen_3_Cross_31580’, ‘Gen_3_Mutant_91_450305’, ‘Gen_3_Mutant_64_445680’, ‘Gen_3_Cross_613103’, ‘Gen_3_Mutant_18_35745’, ‘Gen_3_Cross_366775’, ‘Gen_3_Mutant_18_586750’, ‘Gen_3_Cross_742077’, ‘Gen_3_Mutant_65_697626’, ‘Gen_3_Cross_461049’, ‘Gen_3_Mutant_18_774759’, ‘Gen_3_Mutant_85_116918’, ‘Gen_3_Mutant_78_448425’, ‘Gen_3_Mutant_27_195790’, ‘Gen_3_Mutant_80_851841’, ‘Gen_3_Cross_874104’, ‘Gen_3_Mutant_81_608951’, ‘Gen_3_Mutant_46_935113’, ‘Gen_3_Mutant_93_125851’, ‘Gen_3_Mutant_35_220256’, ‘Gen_3_Mutant_80_951443’]
CONVERTING SMILES TO SDF COMPLETED
CONVERTING SDF TO PDB
Process Process-246:
Traceback (most recent call last):
File “/Users/bhartisingal/Documents/autogrow4-4.0.0/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 /Users/bhartisingal/Documents/autogrow4-4.0.0/Bharti_Covid19/outputfolder/Run_10/generation_3/3D_SDFs/Gen_3_Mutant_51_176862__input1.sdf

During handling of the above exception, another exception occurred:

Traceback (most recent call last):
File “/Users/bhartisingal/opt/anaconda3/lib/python3.7/multiprocessing/process.py”, line 297, in _bootstrap
self.run()
File “/Users/bhartisingal/opt/anaconda3/lib/python3.7/multiprocessing/process.py”, line 99, in run
self._target(*self._args, **self._kwargs)
File “/Users/bhartisingal/Documents/autogrow4-4.0.0/autogrow/operators/convert_files/gypsum_dl/gypsum_dl/Parallelizer.py”, line 666, in worker
result = func(*args)
File “/Users/bhartisingal/Documents/autogrow4-4.0.0/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()
Process Process-245:
Traceback (most recent call last):
File “/Users/bhartisingal/Documents/autogrow4-4.0.0/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 /Users/bhartisingal/Documents/autogrow4-4.0.0/Bharti_Covid19/outputfolder/Run_10/generation_3/3D_SDFs/Gen_3_Cross_485991__input1.sdf

During handling of the above exception, another exception occurred:

Traceback (most recent call last):
File “/Users/bhartisingal/opt/anaconda3/lib/python3.7/multiprocessing/process.py”, line 297, in _bootstrap
self.run()
File “/Users/bhartisingal/opt/anaconda3/lib/python3.7/multiprocessing/process.py”, line 99, in run
self._target(*self._args, **self._kwargs)
File “/Users/bhartisingal/Documents/autogrow4-4.0.0/autogrow/operators/convert_files/gypsum_dl/gypsum_dl/Parallelizer.py”, line 666, in worker
result = func(*args)
File “/Users/bhartisingal/Documents/autogrow4-4.0.0/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 Bharti. Much thanks for your interest in AutoGrow. Would you mind sending me the AutoGrow parameters you’re using? That will help with debugging. We have a theory re. what’s happening, but it will be good to confirm. Take care.

[Bharti]

Hi Dr. Durrant, thank you for your response. Here I have copied the parameters from var file generated. I have been using autogrow with other custom fragments too, I was getting the same error after generation 8/10.
In addition to that unable to draw lineage as it says the parent compound is missing. However, I am providing the same source file which I used for that autogrow run.

“start_a_new_run”: true,
“max_time_mcs_prescreen”: 1,
“max_time_mcs_thorough”: 1,
“min_atom_match_mcs”: 4,
“protanate_step”: false,
“rxn_library”: “all_rxns”,
“rxn_library_file”: “”,
“function_group_library”: “”,
“complementary_mol_directory”: “”,
“number_of_processors”: -1,
“multithread_mode”: “multithreading”,
“selector_choice”: “Rank_Selector”,
“tourn_size”: 0.1,
“top_mols_to_seed_next_generation_first_generation”: 10,
“top_mols_to_seed_next_generation”: 10,
“diversity_mols_to_seed_first_generation”: 10,
“diversity_seed_depreciation_per_gen”: 0,
“filter_source_compounds”: false,
“use_docked_source_compounds”: false,
“num_generations”: 8,
“number_of_crossovers_first_generation”: 50,
“number_of_mutants_first_generation”: 50,
“number_of_crossovers”: 50,
“number_of_mutants”: 50,
“number_elitism_advance_from_previous_gen”: 10,
“number_elitism_advance_from_previous_gen_first_generation”: 10,
“redock_elite_from_previous_gen”: false,
“LipinskiStrictFilter”: false,
“LipinskiLenientFilter”: true,
“GhoseFilter”: false,
“GhoseModifiedFilter”: false,
“MozziconacciFilter”: false,
“VandeWaterbeemdFilter”: false,
“PAINSFilter”: false,
“NIHFilter”: false,
“BRENKFilter”: false,
“No_Filters”: false,
“alternative_filter”: null,
“dock_choice”: “VinaDocking”,
“docking_executable”: null,
“docking_exhaustiveness”: null,
“docking_num_modes”: null,
“docking_timeout_limit”: 120,
“custom_docking_script”: “”,
“scoring_choice”: “VINA”,
“rescore_lig_efficiency”: true,
“custom_scoring_script”: “”,
“max_variants_per_compound”: 5,
“gypsum_thoroughness”: 3,
“min_ph”: 6.4,
“max_ph”: 8.4,
“pka_precision”: 1.0,
“gypsum_timeout_limit”: 10,
“debug_mode”: false,
“reduce_files_sizes”: false,
“generate_plot”: true,
“timeout_vs_gtimeout”: “gtimeout”,

[Jacob Durrant]

Hi Bharti. We recently realized that the latest version of RDKit (one of the python libraries that AutoGrow4/Gypsum-DL uses) has broken backwards compatibility. We made some updates to these programs to address the issue. I don’t know if you’re using the latest version of RDKit, but you might want to try the latest version of AutoGrow4 (4.0.1) in case this bug is affecting your run: https://git.durrantlab.pitt.edu/jdurrant/autogrow4

Take care!

[Author]

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