Binding Pose Metadynamics Panel

Run a series of metadynamics MD simulations on a set of binding configurations of a single ligand in a single binding site, to rank the poses and predict the correct binding pose.

To open this panel, click the Tasks button and browse to Classical Simulation → Binding Pose Metadynamics.

  • Using
  • Features
  • Additional Resources

Using the Binding Pose Metadynamics Panel

The purpose of this panel is to evaluate the stability of poses from a Desmond metadynamics MD simulation, to determine what the correct pose is. The stability is assessed in terms of the fluctuations of the ligand RMSD over the course of the simulation, and the persistence of important contacts between the ligand and the receptor (and any other cofactors or solvent molecules), such as hydrogen bonds and pi interactions. The collective variable for the metadynamics simulation is the ligand RMSD from its initial pose, evaluated after superposition of the binding sites to account for drift. To improve the statistics, several simulations are performed and the results are averaged over the simulations.

The output includes the metadynamics portion of the dynamics as well as a plot with the extension -out.pdf which plots the average value of the collective variable over the simulation.

The Maestro properties returned from the simulation for each ligand (or complex) are:

MetadynamicsBinding CompScore Composite Score linearly combining the MetadynamicsBinding PoseScore and MetadynamicsBinding Persistence scores. Lower values equate to more stable complexes. The equation is PoseScore - 5 * Persistence.
MetadynamicsBinding PoseScore Expectation of the RMSD of the pose over the course of the metadynamics. Lower values equate to more stable complexes.
MetadynamicsBinding Persistence Average persistence of contacts over the course of the metadynamics trajectories. Higher values equate to more stable complexes.
MetadynamicsBinding Persistence HBond Average persistence of HBonds.
MetadynamicsBinding Persistence Pi Average persistence of Pi-Pi stacking and T-Shaped interactions.
MetadynamicsBinding In RMSD Optional RMSD after the relaxation step. This can help identify cases where the relaxation before the metadynamics is materially changing the pose.

Note:

Task validation for ligand ASL now has an atom limit of 500 to accommodate larger ligands.

Binding Pose Metadynamics Panel Features

Use structures from option menu

Choose the structure source for the current task. The structures must be a set of poses from the same ligand, either as protein-ligand complexes or with the receptor followed by the poses (pose-viewer format).

  • Project Table (n selected entries)—Use the entries that are currently selected in the Project Table or Entry List. The number of entries selected is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and select entries.
  • Workspace (n included entries)—Use the entries that are currently included in the Workspace, treated as separate structures. The number of entries in the Workspace is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and include or exclude entries.
  • File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed. The allowed file types are: Maestro files.
Open Project Table button

Open the Project Table panel, so you can select or include the entries for the structure source.

File name text box and Browse button

Enter the file name in this text box, or click Browse and navigate to the file. The name of the file you selected is displayed in the text box.

Range settings

Specify the range of ligands to use from the file, if you selected File as the structure source. To start at a ligand other than the first, set the value in the first text box to the index of the first ligand to use. To end at a ligand other than the last, deselect End and set the index value of the last ligand to use in the second text box.

Structure type options

Select an option for the type of structure source.

  • Receptor-ligand complexes—each structure is a receptor-ligand complex. This is the normal output from an IFD calculation, where the receptor responds to the presence of the ligand.

  • Docked poses—the receptor is the first structure, followed by the ligands. This is the normal output from a Glide calculation, "pose viewer" format.

Binding site ligand option menu

Use this option menu to identify the ligand, if there is more than one ligand-sized molecule in the structure. The ligand-sized molecules are listed on this option menu.

Number of trials per pose text box

Set the number of metadynamics simulations to perform for each pose. Running more than one simulation improves the statistics, but requires more computer time. Current experience suggests that there is no benefit in performing more than 10 simulations per pose.

Job toolbar

Manage job submission and settings. See Job Toolbar for a description of this toolbar.

The Job Settings button opens the Binding Pose Metadynamics - Job Settings Dialog Box, where you can make settings for running the job.

Status bar

The status bar displays information about the current job settings and status for the panel. The settings includes the job name, task name and task settings (if any), number of subjobs (if any) and the host name and job incorporation setting. The job status can include messages about job start, job completion and incorporation.

Use the Reset button to reset the panel to its default settings and clear any data from the panel. You can also reset the panel from the Job toolbar.

The status bar also contains the Help button , which opens the help topic for the panel in your browser. If the panel is used by one or more tutorials, hovering over the Help button displays a button, which you can click to display a list of tutorials (or you can right-click the Help button instead). Choosing a tutorial opens the tutorial topic.

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