Perform Weighted Ensemble MD Analysis

Quick floe search term: CPD A4

This floe performs a range of analyses on weighted ensemble MD simulation data generated by Run a Weighted Ensemble MD Simulation and Continue a Weighted Ensemble MD Simulation floes and evaluates the extent of sampling and structural fluctuations observed during the simulation.

Tip

This job can take 2 hours to complete and cost approximately $20.

Search and Run the Floe in Orion

Locate the floe in Orion

Start by using the left hand vertical navigation tabs on your Orion home page to go to Floe page.

On the Floe page, click on the Floes tab, where you will find the list of the available floes and packages.

Click on a small caret next to Packages (under Filter Floes By section on the left) to expand the list of packages and click on the OpenEye Cryptic Pocket Detection Floes package. This will ensure that the floes listed in the middle of the page are from the Cryptic Pocket Detection package.

From this list, click on the Perform Weighted Ensemble MD Analysis floe, and then click on the blue LAUNCH FLOE button in the bottom right corner of the page to launch the Job Submission Form.

Provide Input Files and Parameters to Run the Floe

• Output path:

  Select the destination for your output data by specifying the Output path.

• Input Data:

  You will need to provide a Protein Sampling Data collection generated by the Run a Weighted Ensemble MD Simulation floe as an input.

• Output Data:

  You can customize the output dataset and collection names under the Output Data options.

• Parameters For Free Energy Maps/Surfaces:

  Advanced parameters to customize the type of weighted ensemble trajectory analysis are given under this section.

  Selection String: Users can define the set of residues on which to perform RMSD and Native Contacts analyses. This selection can be additionally filtered by choosing one of the options given under Atoms selection modifier parameter.

  Atoms selection modifier: If protein (default) is selected, RMSD and Native Contacts calculations will be performed on all heavy atoms of the selected residues. Other options include backbone (backbone heavy atoms), name==CA (C-alpha atoms) and sidechain (side-chain heavy atoms)

  Users can optionally turn off Native Contact Map and/or RMSD Map options using the toggle switch given next to these parameters.

  Apply Weight: This option can be turned off if you wish to ignore the weights (from Weighted Ensemble MD) of the conformations in free energy calculations.

  Maximum Free Energy Value and Number of Histogram Bins adjust the maximum free energy value to be displayed in the maps and the resolution of the free energy profiles, respectively.

• Selection Range For Trajectories:

  Start Iteration: This parameter and End Iteration define the range of iterations to include in the trajectory analyses. The default setting includes all iterations starting from 1. By setting a number greater than 1 for Start Iteration, initial iterations can be excluded from the analysis.

  End Iteration: If left unspecified, the entire simulation dataset is analyzed. You can select a number lower than the total number of iterations for which your weighted ensemble MD simulation was run.

  Stride: By default every frame will be included in the analyses. However, users can set this parameter value between 2 to 4 to read only every stride-th frame during trajectory analyses.

  A4 RMSF Analysis Memory (MB): If your analysis fails due to insufficient memory, you can increase the memory requirement here and rerun the floe.

Job Submission Form

Click on the green Start Job button a the bottom right corner of the page.

Visualize Weighted Ensemble MD Analysis Floe Reports

Access the Floe Reports

When the job is complete, all results will be gathered in a floe report - Weighted Ensemble MD Analysis Floe Report. You can get to this floe report by clicking on the job that you want to inspect.

Under Reports, click on floe report - Weighted Ensemble MD Analysis Floe Report. This will redirect you to an index page which lists two linked reports: Root Mean Squared Fluctuations (RMSF) and Visualisation of weighted ensemble MD analysis. If RMSD Map option was turned off at the time of running the job, you will see only Visualisation of weighted ensemble MD analysis on this page.

Clicking on one of these links will take you to respective analysis reports.

Viewing the floe report from the job page.

Root Mean Squared Fluctuations (RMSF) Report

• Figure 1 shows the per residue RMSF calculation of protein’s C-alpha atoms based on anisotropic network model (ANM) used to derive progress coordinates for the simulation.

• Figure 2 shows the per residue RMSF calculated from the Weighted Ensemble MD simulation data. The plot on left shows RMSF of the backbone atoms for each residue, and the one on the right shows per-residue RMSF for sidechain atoms. Per-residue RMSF values are obtained by averaging over the heavy atoms of a residue. The plots display both weighted (shown in green) and non-weighted (shown in pink) averages of RMSF. For the weighted calculations, conformational weights are obtained from the weighted ensemble MD simulations.

The RMSF floe report page.

Visualisation of weighted ensemble MD analysis Report

• Figures 1 & 2 show the 1-D probability distribution and negative log of the probability distribution for each progress coordinate (normal mode).

• Figure 3 shows the 2-D probability distribution and negative log of the probability distribution projected onto the progress coordinates (normal modes).

• Figure 4 shows the average fraction of native contacts conserved in the simulation projected onto the progress coordinates.

• Figure 5 shows the average root mean square deviation (RMSD) of the conformations projected onto the progress coordinates. The initial protein structure (Spruce-prepped design unit) is used as the reference structure for RMSD as well as the native contacts calculations.

The Weighted Ensemble MD analysis floe report page.