Cryo-EM Map Best Structure Search from WEMD Simulation

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Role-based/Structural Biologist

  • Solution-based/Target Identification/Target Preparation

  • Task-based/Target Prep & Analysis/Protein Preparation

  • Product-based/Molecular Dynamics/WESTPA

Description

This floe generates cryogenic electron microscopy (cryo-EM) density maps for each conformer selected from WEMD simulation trajectories. It also finds the best candidates to match the reference map experiments by calculating correlation coefficients between simulated and experimental maps. Multiple reference maps can be input and matched at the same time.

Promoted Parameters

Title in user interface (promoted name)

Input Data for Simulation

Collection (collection): Protein sampling data generated from previous weighted ensemble MD simulations. Only one WEMD collection is created for a series of WEMD simulations for the same system and setting.

  • Required

  • Type: collection_source

  • Default: wemd_simulation_collection

Input Cryo-EM Maps and Options for Best Structures Search

Cryo-EM Map Resolution (resolution): Resolution of the input cryo-EM maps (angstroms).

  • Required

  • Type: decimal

  • Default: 2.0

Reference Protein Dataset after SPRUCE Preparation (ref_dataset): Input Dataset for Reference Protein (structure must be fit to the input cryo-EM maps).

  • Required

  • Type: data_source

Superposition method (superpose_method): Superposition method to fit simulation structure to reference structure of cryo-EM map.

  • Required

  • Type: string

  • Default: GlobalSequence

  • Choices: [‘GlobalSequence’, ‘SiteSequence’, ‘DDMatrix’, ‘SSE’, ‘SiteHopper’]

Selected Components for Cryo-EM Map (mask_components): Selected components to generate simulated maps from simulation trajectories.

  • Required

  • Type: string

  • Default: [‘protein’, ‘nucleic’, ‘ligand’]

  • Choices: [‘protein’, ‘nucleic’, ‘ligand’, ‘solvent’, ‘metals’, ‘counter_ions’, ‘lipids’, ‘packing_residues’, ‘sugars’, ‘undefined’, ‘cofactors’, ‘excipients’, ‘polymers’, ‘post_translational’, ‘other_proteins’, ‘other_nucleics’, ‘other_ligands’, ‘other_cofactors’]

Cryo-EM Map Files (map_files): Input cryo-EM map files for best structure search (in .mrc format).

  • Required

  • Type: file_in

Resize Cryo-EM Map(s) (resize_map): Toggle on to resize cryo-EM map(s) using reference structure(s) with 10 angstroms of padding.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Masking options for RSCC

Masking Control (masking_control): Toggle on to mask simulated and reference cryo-EM maps.

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Masking Scheme for Reference Cryo-EM Map (masking_scheme_ref): Options for masking reference cryo-EM map: “all”, include everything; “threshold”, density value below the specified value will be masked out; “std”, density value below the specified standard deviations above the mean will be masked out.

  • Type: string

  • Default: threshold

  • Choices: [‘all’, ‘threshold’, ‘std’]

Masking Value for Reference Cryo-EM Map (masking_level_ref): Input value for mask definition: for “threshold”, value below which to mask out; for “std”, standard deviations above the mean below which to mask out.

  • Type: decimal

  • Default: 0.0

Masking Scheme for Simulated Cryo-EM Map (masking_scheme_traj): Options for masking reference cryo-EM map: “all”, include everything; “threshold”, density value below the specified value will be masked out; “std”, density value below the specified standard deviations above the mean will be masked out.

  • Type: string

  • Default: threshold

  • Choices: [‘all’, ‘threshold’, ‘std’]

Masking Value for Simulated Cryo-EM Map (masking_level_traj): Input value for mask definition: for “threshold”, value below which to mask out, for “std”, standard deviation above mean below which to mask out.

  • Type: decimal

  • Default: 0.005

Masking Type for Cryo-EM Maps (masking_type): Options for how to combine the masks for trajectory and reference cryo-EM map: “union”, use the union mask from two maps; “overlap”, use the overlap mask between two maps; “reference”, use only the mask from reference map; “trajectory”, use only the masks from trajectory.

  • Type: string

  • Default: trajectory

  • Choices: [‘union’, ‘overlap’, ‘reference’, ‘trajectory’]

Selections for Output Best Structures

Superpose Control (superpose_ctrl): Toggle on to superpose trajectory onto input reference structure.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Number of Top Candidates for Saving (ntop_out): Number of top candidates for each map to save to dataset.

  • Required

  • Type: integer

  • Default: 5

Output Best Structures for Input Cryo-EM Maps (struct_data_out): Output dataset saves the top N simulation structures for each input cryo-EM maps.

  • Required

  • Type: dataset_out

  • Default: best_structures_dataset

Selection Range for Trajectories

Start Iteration (first_iter): The start iteration of WE segments to be extracted. Leave empty to extract from the first iteration that is available.

  • Type: integer

End Iteration (last_iter): The end iteration of WE segments to be extracted. Leave empty to stop extracting at the last iteration that is available.

  • Type: integer

Endpoint Only (endpoint_only): By default, each WEMD segment has five conformers saved. If True, only the last one is used; if False, all five are used.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Analysis Stride (N) (stride): Skip every N frames during analysis. No valid when the endpoint-only option is on.

  • Type: integer

  • Default: 1

Parameters for Estimating Free Energy Maps/Surfaces

Weight Free Energy Calculation (weight_option): Toggle on to apply WEMD weights when generating free energy maps (default=True).

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Density Distribution Bins (number_bins): Number of bins for plotting density distribution in each dimension.

  • Type: integer

  • Default: 50

Maximum value of free energy (max_free_energy): Maximum value for showing estimated 2D free energy map in colors.

  • Type: decimal

  • Default: 50.0

Outputs for Cryo-EM Map Analysis

None (floe_report_name):

  • Type: string

  • Default: Failure Report

None (analysis_report_title): Title for the analysis report.

  • Type: string

  • Default: Cryo-EM Map Match Report

Output Features for Each WEMD Segment (analysis_data_out): Output dataset saves calculated features from all WEMD segments within selected ranges.

  • Required

  • Type: dataset_out

  • Default: output_features_dataset