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


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


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


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