ABFE¶
This document describes how to run a ABFE simulation using Deep Origin tools.
Prerequisites¶
We assume that we have an initialized and configured Complex object:
from deeporigin.drug_discovery import Complex
sim = Complex.from_dir("/path/to/folder/")
sim.connect()
Here, ABFE requires that the Complex object have an already preppared protein (PDB), and the associated ligands (SDF) are in a docked pose.
Warning
The Complex.from_dir() function only accepts 1 PDB file per directory. This function will throw a warning if it finds more than 1 PDB file per directory.
For more details on how to get started, see Getting Started .
Starting an ABFE run¶
Single ligand¶
To run an end-to-end ABFE workflow on a single ligand, we use:
sim.abfe.run_end_to_end(ligand_ids=["Ligands-1"]) # for example
This queues up a task on Deep Origin. When it completes, outputs will be written to the appropriate column in this database.
Multiple ligands¶
To run an end-to-end ABFE workflow on multiple ligands, we use:
sim.abfe.run_end_to_end(ligand_ids=["Ligands-1", "Ligands-2"])
Omitting the ligand IDs will run ABFE on all ligands in the Complex object.
sim.abfe.run_end_to_end()
Each ligand will be run in parallel on a separate instance.
Job Control¶
Once a job has been submitted, you can track the its status using our built in job tracking:
sim.abfe.show_jobs()
Expected output
Here, the specific stage of the calculation is reported, with the most up-to-date logging information available in the Raw Progress Reports tab.
If we want to cancel a job, first gran the jobID from the Details tab of the Job Control panel:
Expected output
In the above case, the jobID is 4d3536b3-6401-4cb5-ae5b-768daf099d40. Next, we can cancel that job via:
from deeporigin.tools import utils
utils.cancel_runs(['4d3536b3-6401-4cb5-ae5b-768daf099d40'])
Note that this function accepts a list of jobID.
Parameters¶
Viewing parameters¶
The end to end ABFE tool has a number of user-accessible parameters. To view all parameters, use:
sim.abfe._params.end_to_end
Expected output
This will print a dictionary of the parameters used for ABFE, similar to:
{
"abfe": {
"add_fep_repeats": 0,
"amend": "__NO_AMEND",
"annihilate": true,
"atom_mapping_threshold": 0.01,
"em_all": true,
"em_solvent": true,
"emeq_md_options": {
"T": 298.15,
"cutoff": 0.9,
"fourier_spacing": 0.12,
"hydrogen_mass": 2.0,
"Δt": 0.004
},
"fep_windows": [
{
"restraints_A": [
0.0,
0.01,
0.025,
0.05,
0.1,
0.35,
0.5,
0.75,
1.0
]
},
{
"coul_A": [
1.0,
0.8,
0.6,
0.4,
0.2,
0.0
]
},
{
"vdw_A": [
1.0,
0.9,
0.8,
0.7,
0.6,
0.5,
0.4,
0.3,
0.2,
0.1,
0.0
]
}
],
"mbar": 1,
"npt_reduce_restraints_ns": 2.0,
"nvt_heating_ns": 1.0,
"prod_md_options": {
"T": 298.15,
"barostat": "MonteCarloBarostat",
"barostat_exchange_interval": 500,
"cutoff": 0.9,
"fourier_spacing": 0.12,
"hydrogen_mass": 2.0,
"integrator": "BAOABIntegrator",
"Δt": 0.004
},
"repeats": 1,
"run_name": "binding",
"skip_emeq": "__NO",
"softcore_alpha": 0.5,
"steps": 1250000,
"system": "complex",
"test_run": 0,
"thread_pinning": 0,
"thread_pinning_offset": 0,
"threads": 0,
"workers": 0
},
"complex_prep": {
"include_ligands": 1,
"include_protein": 1,
"sysprep_params": {
"charge_method": "bcc",
"do_loop_modelling": false,
"force_field": "ff14SB",
"is_lig_protonated": true,
"is_protein_protonated": true,
"keep_waters": true,
"lig_force_field": "gaff2",
"ligand_res_names": [
"LIG"
],
"padding": 1.0,
"save_gmx_files": false
},
"test_run": 0,
"thread_pinning": 0,
"thread_pinning_offset": 0
},
"emeq": {
"amend": "__NO_AMEND",
"em_all": true,
"em_solvent": true,
"emeq_md_options": {
"T": 298.15,
"cutoff": 0.9,
"fourier_spacing": 0.12,
"hydrogen_mass": 2.0,
"Δt": 0.004
},
"from_run": "__USE_SYSTEM",
"npt_reduce_restraints_ns": 0.2,
"nvt_heating_ns": 0.1,
"test_run": 0,
"thread_pinning": 0,
"thread_pinning_offset": 0,
"threads": 0
},
"ligand_prep": {
"include_ligands": 1,
"include_protein": 0,
"sysprep_params": {
"charge_method": "bcc",
"do_loop_modelling": false,
"force_field": "ff14SB",
"is_lig_protonated": false,
"is_protein_protonated": false,
"keep_waters": false,
"lig_force_field": "gaff2",
"padding": 1.0,
"save_gmx_files": false
},
"test_run": 0,
"thread_pinning": 0,
"thread_pinning_offset": 0
},
"md": {
"amend": "__NO_AMEND",
"continue": 0,
"from_run": "__USE_SYSTEM",
"md_options": {
"T": 298.15,
"barostat": "MonteCarloBarostat",
"barostat_exchange_interval": 500,
"cutoff": 0.9,
"fourier_spacing": 0.12,
"hydrogen_mass": 2.0,
"integrator": "BAOABIntegrator",
"Δt": 0.004
},
"run_name": "md",
"steps": 250000,
"test_run": 0,
"thread_pinning": 0,
"thread_pinning_offset": 0,
"threads": 0
},
"solvation": {
"add_fep_repeats": 0,
"amend": "__NO_AMEND",
"annihilate": true,
"atom_mapping_threshold": 0.01,
"em_all": true,
"em_solvent": true,
"emeq_md_options": {
"T": 298.15,
"cutoff": 0.9,
"fourier_spacing": 0.12,
"hydrogen_mass": 2.0,
"Δt": 0.004
},
"fep_windows": [
{
"coul_A": [
1.0,
0.8,
0.6,
0.4,
0.2,
0.0
]
},
{
"vdw_A": [
1.0,
0.9,
0.8,
0.7,
0.6,
0.5,
0.4,
0.3,
0.2,
0.1,
0.0
]
}
],
"mbar": 1,
"npt_reduce_restraints_ns": 0.2,
"nvt_heating_ns": 0.1,
"prod_md_options": {
"T": 298.15,
"barostat": "MonteCarloBarostat",
"barostat_exchange_interval": 500,
"cutoff": 0.9,
"fourier_spacing": 0.12,
"hydrogen_mass": 2.0,
"integrator": "BAOABIntegrator",
"Δt": 0.004
},
"repeats": 1,
"skip_emeq": "__NO",
"softcore_alpha": 0.5,
"steps": 300000,
"test_run": 1,
"thread_pinning": 0,
"thread_pinning_offset": 0,
"threads": 0,
"workers": 0
}
}
Modifying parameters¶
Any of these parameters are modifiable using dot notation. For example, to change the number of steps in the MD step, we can use:
sim.abfe._params.end_to_end.md.steps = 500000
Using test_run¶
The test run parameter can be used to run ABFE for a short number of steps, to verify that all steps execute quickly. This should not be used to run production simulations.
To set the test run parameter to 1, we can use:
from deeporigin.utils.core import set_key_to_value
set_key_to_value(sim.abfe._params.end_to_end, "test_run", 1)
Results¶
Viewing results¶
After initiating a run, we can view results using:
sim.abfe.show_results()
This shows a table similar to:
Expected output
Exporting results for analysis¶
These results can be exported for analysis using:
df = sim.abfe.get_results()
df
Expected output
| Binding | Solvation | AnalyticalCorr | Std | Total | ID | File | r_exp_dg | SMILES |
|---|---|---|---|---|---|---|---|---|
| 16.23 | -27.53 | -7.2 | 0.0 | -36.50 | Ligands-1 | brd-2.sdf | -9.59 | [H]C1=C([H])C(C(=O)N(C([H])([H])[H])C([H])([H])[H])=C([H])C(C2=C([H])N(C([H])([H])[H])C(=O)C3=C2C([H])=C([H])N3[H])=C1[H] |
| -454.99 | -722.01 | -7.58 | 0.0 | -259.44 | Ligands-2 | brd-3.sdf | -7.09 | [H]C([H])=C([H])C([H])([H])N1C(=O)C2=C(C([H])=C([H])N2[H])C(C2=C([H])C([H])=C([H])C(C(=O)N(C([H])([H])[H])C([H])([H])[H])=C2[H])=C1[H] |
| -600.31 | -1354.79 | -7.47 | 0.0 | -747.00 | Ligands-3 | brd-4.sdf | -8.64 | [H]C1=C([H])C(C(=O)N(C([H])([H])[H])C([H])([H])[H])=C([H])C(C2=C([H])N(C([H])([H])/C([H])=C([H])C([H])([H])[H])C(=O)C3=C2C([H])=C([H])N3[H])=C1[H] |