A3a. Protein Sampling (for Cryptic Pockets): Run a Weighted Ensemble MD Simulation¶
Category Paths
Follow one of these paths in the Orion user interface, to find the floe.
Product-based/Molecular Dynamics
Solution-based/Virtual-screening/Target Preparation
Solution-based/Hit to Lead/Target Preparation/Enhanced Sampling
Solution-based/Target Identification/Target Preparation/Pocket Detection
Solution-based/Hit to Lead/Target Preparation/Cryptic Pocket Detection
Role-based/Computational Chemist
Task-based/Target Prep & Analysis/Pocket Detection
Description
This floe uses weighted ensemble molecular dynamics to sample the conformational dynamics of a target protein. Sampling is enhanced along a given set of normal modes.
Promoted Parameters
Title in user interface (promoted name)
Weighted Ensemble Parameters
Iterations (iterations): Number of iterations for the WE simulation. Suggested values: 50 iterations (total) for proteins with <200 residues; 100 iterations (total) for proteins with <600 residues.
Required
Type: integer
Default: 50
Iteration Interval (tau) (iteration_interval): Length of each WE iteration in picoseconds.
Type: decimal
Default: 100.0
Advanced Weighted Ensemble Parameters
Report Interval (dtau) (report_interval): Trajectories saving interval for the WE run in picoseconds.
Type: decimal
Default: 20.0
Number of Bins per Dimension (nbins): The number of bins along each normal mode. Either a single value or a sequence of values (one for each mode) may be provided. Bin placement is controlled by the Minimal Adaptive Binning (MAB) scheme (P.A. Torrillo, A.T. Bogetti, L.T. Chong, J. Phys. Chem. A 2021, 125, 7, 1642–1649).
Required
Type: integer
Default: [10]
Trajectories Per Bin (walkers_per_bin): Number of trajectories per bin for the WE simulation.
Type: integer
Default: 10
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
Inputs
Protein Normal Mode Records (modes_in): One or two records specifying the normal modes along which to promote sampling. These records come from a ‘Protein Normal Modes Dataset’ output generated by ‘A2. Protein Sampling (for Cryptic Pockets): Calculate Normal Modes’.
Required
Type: data_source
Solvated and Equilibrated Design Unit (data_in): This is the ‘Solvated and Equilibrated Design Unit’ output dataset from the ‘A1. Protein Sampling (for Cryptic Pockets): Solvate and Equilibrate Target Protein’ floe.
Required
Type: data_source
Outputs
Output Dataset (data_out): Output dataset containing the current iteration number, simulation settings, and a reference design unit. This dataset contains only 1 record, and can be viewed on the Orion Analyze page to track the total number of iterations that have been completed.
Required
Type: dataset_out
Default: Protein Sampling Dataset
Output Collection (collection_out): Name of the collection in which to store the simulation output.
Required
Type: collection_sink
Default: Protein Sampling Data Collection
Reference Structure File (ref_file): Name of the file to create for storing the reference structure. The file name extension must be “.h5”.
Required
Type: file_out
Default: ref.h5
Failure Report (fail_report): Output report to generate upon failure.
Type: string
Default: Protein Sampling Failure Report