not binding to the target protein pocket

[gry-613]

Hello, I have set a specific center binding (the centroid of the small molecule in the original crystal structure) and box size when using AutoDock Vina for docking. However, the small molecule is not binding to the target protein pocket in the resulting docking poses. I have tried several times, including modifying the box size from 10 to 20, but the generated molecules are still not in the binding pocket. What suggestions do you have? looking forward for your answer.

TOML file:
run_type = "staged_learning"
use_cuda = true
tb_logdir = "rl_try_1"
json_out_config = "_try_1.json"

[parameters]
use_checkpoint = false
smiles_file = "fix_leu_val.smi"
summary_csv_prefix = "leu_val_rl.csv"
agent_file = "/disk1/finishing/07_mcl-1_bh3/REINVENT4/priors/linkinvent.prior"
prior_file = "/disk1/finishing/07_mcl-1_bh3/REINVENT4/priors/linkinvent.prior"

batch_size = 128
unique_sequences = true
randomize_smiles = true

[learning_strategy]

type = "dap"
sigma = 128
rate = 0.0001

[diversity_filter]

type = "IdenticalMurckoScaffold"
bucket_size = 50
minscore = 0.4
minsimilarity = 0.4
penalty_multiplier = 0.5

[[stage]]
chkpt_file = 'test_1.chkpt'
termination = "simple"
max_score = 0.6
min_steps = 25
max_steps = 100

[stage.scoring]
type = "geometric_mean"

[[stage.scoring.component]]
[stage.scoring.component.Maize]
[[stage.scoring.component.Maize.endpoint]]
name = "docking into 4bpj grid"
weight = 1
params.executable = "/disk2/gry/anaconda_install_pack/install_path/envs/maize/bin/maize"
params.workflow = "/disk1/finishing/07_mcl-1_bh3/maize-contrib/workflows/mai/reinvent/vina.yml"
search_range = [12, 12, 12]
search_center = [6.810, 28.487, 11.856]
params.debug = true
params.keep = true
params.config = "test_config.toml"
params.parameters.receptor = "/disk1/finishing/07_mcl-1_bh3/REINVENT4/configs/toml/try_1_leu_val/4bpj_mcl-1.pdbqt"
params.log = "maize_worfklow_docking.log"
transform.type = "reverse_sigmoid"
transform.high = -7
transform.low = -13.5
transform.k = 0.2

[[stage.scoring.component]]
[stage.scoring.component.QED]
[[stage.scoring.component.QED.endpoint]]
name = "QED"
weight = 1

config file:
[batch]
system = "local"
walltime = "24:00:00"

[vina]
commands.vina = "/disk1/finishing/07_mcl-1_bh3/autodock_vina_1_1_2_linux_x86/bin/vina"

[vinascore]
commands.vina = "/disk1/finishing/07_mcl-1_bh3/autodock_vina_1_1_2_linux_x86/bin/vina"

vina.yml file:
name: vina

nodes:

• name: smiles
  type: ReinventEntry
• name: embed
  type: Smiles2Molecules
• name: dock
  type: Vina
• name: rnv
  type: ReinventExit
• name: void
  type: Void
• name: isocopy
  type: Copy
• name: bestisomerfilter
  type: BestIsomerFilter
• name: saveligs
  type: SaveSingleLibrary

channels:

• sending:
  smiles: out
  receiving:
  embed: inp
• sending:
  embed: out
  receiving:
  dock: inp
• sending:
  dock: out
  receiving:
  isocopy: inp
• sending:
  isocopy: out
  receiving:
  rnv: inp
• sending:
  isocopy: out
  receiving:
  bestisomerfilter: inp
• sending:
  bestisomerfilter: out
  receiving:
  saveligs: inp
• sending:
  smiles: out_metadata
  receiving:
  void: inp

parameters:

• name: inp
  map:

  • smiles: data

• name: out
  map:

  • rnv: data

• name: receptor
  map:

  • dock: receptor

• name: search_center
  value: [6.810, 28.487, 11.856]
  map:

  • dock: search_center

• name: search_range
  value: [12, 12, 12]
  map:

  • dock: search_range

• name: n_jobs
  value: 20
  map:

  • dock: n_jobs

• name: save_location
  value: saved_ligands.sdf
  map:

  • saveligs: file

• name: save_poses
  map:

  • saveligs: active

• name: exhaustiveness
  value: 8
  map:

  • dock: exhaustiveness

• name: num_poses
  value: 5
  map:

  • dock: n_poses

[halx]

Please use quoting, the "<>" icon, for config data, code, etc.

Your question is not REINVENT related. Have you made sure that you can actually dock successfully with you docking program?

[gry-613]

Thanks for your answer. The problem has been solved. It was due to an issue with my pdbqt file.