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 the Permeability - Analyze Permeability Simulation Floe on the output collection 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

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 WEMD simulation.

  • Required

  • Type: integer

  • Default: 5

Number of Frames Per Iteration (frames_per_iteration): Number of frames saved in each WE iteration.

  • Type: integer

  • Default: 5

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

  • Type: decimal

  • Default: 100.0

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.

  • Required

  • Type: decimal

  • Default: -310.0

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. The OpenFF >=1.3.1 and Custom force fields may be augmented with bespoke force field parameters by turning on ‘Use Bespoke Parameters When Available’ and providing SMIRNOFF format parameters on the input record.

  • Required

  • 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’, ‘OpenFF_2.2.0’, ‘Smirnoff99Frosst’, ‘Custom’]

Time (prod_time): Length of the simulation for system preparation 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

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

Collection Name (collection_name): Name of the collection to create

  • 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’]

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