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 (Tutorial: how to select normal modes as progress coordinates ). Note that the job can cost a few thousand dollars if the number of iterations for the simulation is too high (>500).

Promoted Parameters

Title in user interface (promoted name)

Input Data

Protein Normal Mode Records (mode_data_in): One more two records containing the normal modes along which to promote sampling. These records come from a ‘’Protein Normal Modes’’ output generated by ‘Calculate Normal Modes’. By default, the top two modes from the input dataset will be selected. If you wish to select specific modes, follow the tutorial linked in the floe description above.

  • Required

  • Type: data_source

Solvated and Equilibrated Protein (du_data_in): The ‘Solvated and Equilibrated Protein’ dataset output from the ‘Solvate and Equilibrate Target Protein’ floe.

  • Required

  • Type: data_source

Output Data

Output Dataset (a3_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 Summary Table

Collection Name (a3a_collection_name): Name of the collection to create

  • Required

  • Type: collection_sink

  • Default: Protein Sampling Data

Failure Report (failure_report): Output report to generate upon failure.

  • Type: string

  • Default: Protein Sampling Failure Report

Weighted Ensemble Parameters

Iterations (a3a_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. Note that the job can cost a few thousand dollars if this parameter is too high (>500).

  • Required

  • Type: integer

  • Default: 50

Iteration Interval (Tau) (a3a_iteration_interval): Length of each WE iteration in picoseconds.

  • Type: decimal

  • Default: 100.0

Advanced Weighted Ensemble Parameters

Number of Frames Per Iteration (a3a_frames_per_iteration): Number of frames saved in each WE iteration.

  • Type: integer

  • Default: 5

Number of Bins per Dimension (a3a_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 (a3a_walkers_per_bin): Number of trajectories per bin for the WEMD simulation.

  • Required

  • Type: integer

  • Default: 10

Smallest Allowed Weight (Log) (a3a_smallest_allowed_log_weight): The smallest allowed weight for splitting in logarithmic scale.

  • Required

  • Type: decimal

  • Default: -310.0

Log Verbosity (verbosity): verbose level

  • Type: string

  • Default: debug

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