Not creating ranked ligand file during lead optimization in generation 0

[Taylor Witte]

Hi!
I am doing lead optimization. I loaded ligands that I already generated in autogrow from a smi file and they successfully docked and I have docking scores from the docking output txt file in the PDB file of generation 0. However, the generation_0_ranked.smi file is empty. The generation_0.smi, generation_0_to_convert.smi and the files in the SEEDFolder and PDB folder are full.
Error Output file:
Traceback (most recent call last):
File "RunAutogrow.py", line 675, in <module>
AutogrowMainExecute.main_execute(vars)
File "/home/witte.t/autogrow4/autogrow/autogrow_main_execute.py", line 83, in main_execute
smile_file_new_gen, new_gen_ligands_list = operations.populate_generation(vars, current_generation_number)
File "/home/witte.t/autogrow4/autogrow/operators/operations.py", line 75, in populate_generation
vars, generation_num
File "/home/witte.t/autogrow4/autogrow/operators/operations.py", line 691, in get_complete_list_prev_gen_or_source_compounds
raise Exception(printout)
Exception:
There were no available ligands in previous generation ranked ligand file.
Check formatting or if file has been moved.

End of Output file:
Begin Ranking and Saving results

Completed Ranking and Saving results

Deleting temporary files and directories

Finished generation 0
/home/witte.t/autogrow4/practice_optimization/Run_6/generation_1/

There were no available ligands in previous generation ranked ligand file.
Check formatting or if file has been moved.

For Reference Input Variables:
python RunAutogrow.py –filename_of_receptor ./MPro_editted_pdb/mpro_prepped.pdb –center_x -19.4915 –center_y -0.518 –center_z 12.1245 –size_x 22.6 –size_y 24.5 –size_z 22.9 –source_compound_file ./ligands/autogrowligands.smi –root_output_folder ./practice_optimization –number_of_mutants 30 –number_of_crossovers 30 –top_mols_to_seed_next_generation 15 –number_elitism_advance_from_previous_gen 15 –number_elitism_advance_from_previous_gen_first_generation 30 –diversity_seed_depreciation_per_gen 10 –num_generations 12 –conversion_choice ObabelConversion –obabel_path /shared/centos7/openbabel/2.4.1/bin/obabel –mgltools_directory /home/witte.t/autogrow4/mgltools/mgltools_x86_64Linux2_1.5.6 –number_of_processors -1 –scoring_choice VINA –LipinskiLenientFilter –start_a_new_run –rxn_library all_rxns –selector_choice Rank_Selector –gypsum_timeout_limit 500 –dock_choice VinaDocking –max_variants_per_compound 5 –redock_elite_from_previous_gen False –generate_plot True –reduce_files_sizes False –use_docked_source_compounds True –prepare_receptor4.py True> ./practice_optimization/output_file_run3b.txt 2> ./practice_optimization/error_file_run3b.txt

Best,
Taylor

[Jacob Durrant]

Hi Taylor. Much thanks for your interest in AutoGrow4. The error might occur when none of the compounds of one generation pass the user-specified filters. You could try increasing the number of crossovers, mutants, etc., to give the program more chances to generate acceptable compounds for advancing to the next generation. Another thing to try is to remove the -LipinskiLenientFilter parameter.

If you’d like to debug whether this error is related to AutoGrow4 installation, you could try using this test file that is included with the AutoGrow4 download: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/blob/4.0.3/sample_sub_scripts/sample_submit_autogrow.json

You could also use the docker container if you’re having installation problems: https://git.durrantlab.pitt.edu/jdurrant/autogrow4/-/tree/4.0.3/docker

The error you posted makes me think it’s more a result of the parameters you’re using than an installation error, though.

Hope this helps,

Jacob

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