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
A floe that simulates the passive membrane permeation of a drug-like molecule using the Weighted Ensemble enhanced sampling strategy. Note that this floe only performs the simulation and does not yield a permeability coefficient. Run the Permeability Analysis Floe on the dataset generated by this floe to estimate the permeability coefficient. By default, the simulation is set up to run for 500 iterations which may cost about a few thousand dollars.
Promoted Parameters
Title in user interface (promoted name)
Weighted Ensemble Parameters
Iterations (iterations): Number of iterations for the WESTPA simulation.
Required
Type: integer
Default: 500
Iteration Interval (tau) (iteration_interval): Length of each WESTPA iteration in picoseconds.
Type: decimal
Default: 100.0
Restart Simulation (restart): Restart the WE simulation from the beginning.
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.
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 WESTPA simulation.
Type: integer
Default: 5
Report Interval (dtau) (report_interval): Trajectories saving interval for the WESTPA 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.
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.
Type: decimal
Default: 0.75
Bin Size (Membrane) (bin_size_membrane): Bin size in membrane (Angstrom).
Type: decimal
Default: 0.5
Bin Size (Water) (bin_size_water): Bin size in water (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
Miscellaneous Parameters
Log Verbosity (verbosity): The level of logging verbosity.
Type: string
Default: debug
Choices: [‘error’, ‘warning’, ‘info’, ‘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