Permeability - Run Permeability Simulation

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Solution-based/Hit to Lead/Properties/Permeability

  • Solution-based/Small Molecule Lead-opt/ADME & Tox/Permeability

  • Product-based/Molecular Dynamics/WESTPA

  • Product-based/Molecular Dynamics/OpenMM

  • Task-based/Molecular Dynamics

  • Task-based/ADME & Tox Assessment

Description

The floe is designed to simulate the passive permeation of a drug-like small molecule rather than a macrocycle or other very large and flexible molecule using the Weighted Ensemble enhanced sampling strategy.

Note that this floe only performs the simulation on one molecule/record at a time and does not yield a permeability estimate. Run Permeability - Analyze Permeability Simulation on the output dataset generated by this floe to calculate the permeability coefficient. By default, the simulation is set up to run for 500 iterations, which may cost a few thousand dollars.

Promoted Parameters

Title in user interface (promoted name)

Weighted Ensemble Parameters

Iterations (iterations): Number of iterations for the WE simulation.

  • Required

  • Type: integer

  • Default: 500

Iteration Interval (tau) (iteration_interval): Length of each WE iteration in picoseconds.

  • Type: decimal

  • Default: 100.0

Restart Simulation (restart): Restart the WE simulation from the beginning.

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Reweighting (reweighting): Reweight the trajectory segments to reduce the relaxation time in steady-state simulations using the WESS method. This parameter will be set to the value specified here when resuming a simulation.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Number of Basis States (n_basis): A set of Omega conformers used as input to permeability.

  • Required

  • Type: integer

  • Default: 20

MAB (mab): Enable the Minimal, Adaptive Binning (MAB) scheme.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Advanced Weighted Ensemble Parameters

Trajectories Per Bin (walkers_per_bin): Number of trajectories per bin for the WE simulation.

  • Type: integer

  • Default: 5

Report Interval (dtau) (report_interval): Trajectories saving interval for the WE run in picoseconds.

  • Type: decimal

  • Default: 20.0

Reweighting Period (reweighting_period): The period of reweighting the trajectory segments in terms of the number of iterations. No reweighting when set to 0. This parameter will be set to the value specified here when resuming a simulation.

  • Required

  • Type: integer

  • Default: 50

Reweighting Window Size (reweighting_window): The fraction of previous iterations used for estimating the transition rates for reweighting. This parameter will be set to the value specified here when resuming a simulation.

  • Required

  • Type: decimal

  • Default: 0.75

Smallest Allowed Weight (Log) (smallest_allowed_log_weight): The smallest allowed weight for splitting in logarithmic scale. Left empty to use WESTPA’s default value.

  • Type: decimal

Grouping History Length (group_history_length): The number of iterations that walkers share in order to be put

into the same group. Grouping is disabled if empty.

  • Type: integer

  • Default: 10

Bin Size (Membrane) (bin_size_membrane): The width of WE bins along z in membrane (Angstrom).

  • Type: decimal

  • Default: 0.5

Bin Size (Water) (bin_size_water): The width of WE bins along z in (Angstrom).

  • Type: decimal

  • Default: 2.0

MAB Bin Size (Membrane) (mab_bin_size_membrane): The maximal bin size (Angstrom) for the MAB scheme in membrane.

  • Type: decimal

  • Default: 1.5

MAB Bin Size (Water) (mab_bin_size_water): The maximal bin size (Angstrom) for the MAB scheme in water.

  • Type: decimal

  • Default: 3.0

System Preparation Parameters

Ligand Forcefield (ligand_ff): Force field to be applied to the ligand

  • Type: string

  • Default: OpenFF_1.3.1

  • Choices: [‘Gaff_1.81’, ‘Gaff_2.11’, ‘OpenFF_1.1.1’, ‘OpenFF_1.2.1’, ‘OpenFF_1.3.1’, ‘OpenFF_2.0.0’, ‘Smirnoff99Frosst’]

Time (prod_time): Length of the simulation for system prepapration in nanoseconds

  • Type: decimal

  • Default: 0.1

Temperature (temperature): Temperature (Kelvin)

  • Type: decimal

  • Default: 308.0

Hydrogen Mass Repartitioning (hmr): Give hydrogens more mass to speed up the preparation

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Preparation CPU Count (prep_cpu_count): The number of CPUs to run the preparation cubes (energy minimization, etc.)

  • Type: integer

  • Default: 8

Preparation Only (prep_only): Prepare the system only without running the WESTPA simulation

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Inputs

Input Dataset (in): The dataset(s) to read records from

  • Required

  • Type: data_source

Outputs

Output Dataset (out): Output dataset to write to

  • Required

  • Type: dataset_out

  • Default: Permeability Simulation

Output Collection (collection_out): Name of the collection in which to store the simulation output.

  • Required

  • Type: collection_sink

  • Default: Permeability Simulation Data

Failure Report (fail_report): Output report to generate upon failure

  • Type: string

  • Default: Permeability Simulation Failure Report

Miscellaneous Parameters

Log Verbosity (verbosity): verbose level

  • Type: string

  • Default: debug

  • Choices: [‘info’, ‘warning’, ‘error’, ‘debug’, ‘ddebug’]

Spot Policy (spot_policy): Control cube placement on spot market instances

  • Type: string

  • Default: Preferred

  • Choices: [‘Allowed’, ‘Preferred’, ‘NotPreferred’, ‘Prohibited’, ‘Required’]

Cleanup (cleanup): Clean up intermediate data. The output record can still be used for resuming a simulation or analysis.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Deep Cleanup (deep_cleanup): Remove WESTPA data to save space for permeability results. WARNING: if this option is turned on, the output record cannot be used by the analysis floe.

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Additional Information

Reference Permeability Coefficient (Logarithmic, Optional) (ref_perm): This can be a value determined by an experiment or determined by other methods as a reference

for comparison. The reference value should have a unit of cm/s and then converted to the log scale. An error can be included in a pair of parentheses, if available. Example input: -6.0 (0.1). Leave the parameter empty to not change it.

  • Type: string

Reference Permeability Coefficient Source (Optional) (ref_src): Source of the reference permeability coefficient, which can be the type of the experiment or

the name of the method that used to determine permeability. Leave the parameter empty to not change it.

  • Type: string

Identification Number for the Molecule (Optional) (mol_id): This can be any identification number (e.g., CHEMBL ID) associated with the molecule.

Leave the parameter empty to not change it.

  • Type: string

Molecule Name (Optional) (mol_name): The name for the molecule. Leave the parameter empty to not change it.

  • Type: string