Metadynamics Panel

Run a metadynamics MD simulation for one or more collective variables.

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

Overview
Using
Features
Additional Resources

Overview of Metadynamics

Metadynamics is an enhanced sampling method which enhances sampling of the underlying free energy space by biasing against previously-visited values of user-specified collective variables. The biasing is achieved by dropping kernels at the current location of the simulation in the phase space of the collective variables. This history-dependent potential encourages the system to explore new values of the collective variables, and the accumulation of potential allows the system to cross potential barriers much more quickly than would occur in standard dynamics.

The implementation of metadynamics in Desmond records the position history using a metadynamics accumulator: a growable n-dimensional kernel density function which uses Gaussian kernel functions ("Hills") located at previously visited locations. The basic form of a Metadynamics Accumulator in Desmond is:

where H_i and σ_i correspond to the height and width of the Gaussian function set by the Height and Width text boxes, respectively.

Using the Metadynamics Panel

Metadynamics is a technique in which the potential for one or more chosen variables ("collective variables") is modified by periodically adding a repulsive potential of Gaussian shape at the location given by particular values of the variables. These repulsive Gaussians eventually fill up the well that is being sampled, and force the calculation to sample elsewhere. At certain points in the simulation, the sum of the Gaussians and the free-energy surface (FES) becomes flat, and therefore the sum of Gaussians is the negative image of the FES.

The parameters that control the accuracy of the simulation are the height and width of the Gaussian potential and the interval at which the Gaussians are added. The accuracy of the results is inversely proportional to the height for a given interval for addition of the Gaussian. However, if smaller heights are used, the simulation takes longer. The accuracy of the results increases as the time interval increases, but the simulation time also increases. The accuracy is not very sensitive to the ratio of the height to the interval, but smaller values of this ratio increase the accuracy. The width of the Gaussian should be roughly 1/4 to 1/3 of the average fluctuations of the collective variable during a free MD run.

To set up a collective variable,

Select an option for the type of variable: Distance, Angle, or Dihedral.

More flexible definitions can only be made from the command line.
Select an option for the atoms that define the collective variable:
- Specify atoms—specify the variable in terms of individual atoms.
- Specify center of mass—specify the variable in terms of the centers of mass of collections of atoms (e.g. residues in a loop). This is useful for examining larger scale motions.
Pick the atoms needed to define the collective variable.
- Specify atoms—Select Pick atoms then pick the required number of atoms in the Workspace. The atom numbers are listed in the AtomN text boxes as you pick.
- Specify center of mass—Pick atoms in the Workspace, then click Get from Selection. The ASL expression for the atoms is entered in the Group N text box, and the next text box is selected. Repeat the process for each group box.
Set the width of the Gaussian in the Width text box.
(Optional) For distance variables, you can place a barrier (“wall”) at a given distance in the Wall at text box.

Introducing a wall prevents the system from moving too far in the direction defined by the collective variable.
Click Add to add the collective variable to the table.

To remove a variable from the simulation, select it in the table and click Remove. Setting up more than two collective variables can create sampling problems.

In the Simulation section, you can make settings for the metadynamics job. The settings for the simulation time, recording interval, ensemble class and model system relaxation are the same as for a molecular dynamics simulation. The default ensemble for metadynamics is NPT.

To write out the input file and a script for running the job from the command line, click the arrow next to the Settings button and choose Write. For information on command usage and options, see multisim Command Help.

Note: Metadynamics simulations are not supported for coarse-grained model systems.

Model system section

In this section, you select the model system that you will use for the simulation. A valid model system must contain both the coordinates of the particles and the force field parameters. A file of a valid model system normally has the .cms extension. You can use the System Builder Panel to prepare the model system for any structure that you have. If you want to build an amorphous structure from scratch, you can use the Disordered System Builder Panel to create a model system.

The option menu offers two choices for the source of the model system:

Load from Workspace—Load the model system from the Workspace. When you choose this option, the Load button is displayed to the right of the menu. Click this button to load the model system.
Import from file—Import the model system from a file. When you choose this option, a text box and Browse button are displayed to the right of the menu. You can enter the name of the file in the text box, or click Browse and navigate to the file.

You can choose to import a model system file (.cms) or a checkpoint file (.cpt).

If you import a model system file, it must contain a model system that has already been prepared. When the file is imported, a message about the system is displayed below the option menu.

If you import a checkpoint file, most of the panel controls are unavailable. The purpose of the checkpoint file is to restart an interrupted simulation, so the parameters of the simulation cannot be altered. You can change the total simulation time, and then start the job.

Simulation section

Collective variable type options

Select the type of collective variable to use for the sampled degree of freedom.

AtomN text boxes

These text boxes display the atom number of the atoms picked for the collective variable, and are displayed when Specify atoms is selected.

Width text box

Width (rms width) of the repulsive Gaussian potential, in angstroms or degrees. The width should be roughly 1/4 to 1/3 of the average fluctuations of the collective variable during a free MD run. The default values are 0.05 Å for distances, 2.5° for angles, and 5° for dihedrals.

Wall at text box

Distance along the collective variable at which a barrier is placed. Introducing a wall prevents the system from moving too far in the direction defined by the collective variable. Only applies to distance variables.

Pick atoms option

Select this option to pick atoms in the Workspace for the collective variable: two for a distance, three for an angle, and four for a dihedral.

If you have changed the Workspace content after loading a model system, you must ensure that the Workspace contains only the model system you loaded before picking.

Add and Remove buttons

Add the collective variable defined above to the table, or remove the selected variable from the table.

Collective variable table

This table lists the collective variable atom numbers with their parameters. You can select a single row to remove from the table. The table is noneditable.

Simulation time text boxes

Specify the total time of the simulation, in ns, in the total text box. Changing the total simulation time changes the trajectory recording interval, to maintain a maximum of 1000 frames in the trajectory.

The elapsed text box displays the amount of time the simulation has already run, if you are restarting a simulation. For new simulations it should contain zero. This text box cannot be edited.

Recording interval text boxes

Specify the recording interval for the energy and the trajectory, in ps, in the energy and trajectory text boxes. Values entered in these text boxes are rounded to an integer multiple of the far time step size. By default, the far time step size is 0.006 ps. This time step size is set in the Integration tab of the Molecular Dynamics - Advanced Options Dialog Box, in the RESPA integrator section. If you adjust the trajectory recording interval, the number of frames is updated.

Approximate number of frames text box

Specify the approximate number of frames in the trajectory. This value is coupled with the recording interval for the trajectory and the simulation time: the number of frames times the trajectory recording interval is the total simulation time. If you adjust the number of frames, the recording interval is modified.

Ensemble class option menu

Choose the ensemble class from this option menu. The following classes are available:

NVE—constant particle number (N), volume (V) and energy (E). This class represents the microcanonical ensemble.
NVT—constant particle number (N), volume (V) and temperature (T). This class represents the canonical ensemble.
NPT—constant particle number (N), pressure (P) and temperature (T). This class is an isothermal-isobaric ensemble, the common experimental conditions.
NPAT—constant particle number (N), pressure (P), lateral surface area (A), and temperature (T). This class is an isothermal-isobaric ensemble with constant normal pressure and lateral surface area i.e. the pressure coupling is nonisotropic.
NPγT—constant particle number (N), pressure (P), lateral surface tension (γ), and temperature (T). This class represents an isothermal-isobaric ensemble with constant normal pressure and lateral surface tension, i.e. the pressure coupling is nonisotropic.

The last two ensembles are often used for membrane-containing systems. Fixing the surface area or surface tension helps to ensure that the simulation box does not deform significantly in the plane of the membrane while the pressure is applied normal to the membrane surface.

Height text box

Height of the repulsive Gaussian potential. The accuracy of the results is inversely proportional to the height for a given interval for addition of the Gaussian. However, if smaller heights are used, the simulation takes longer. The accuracy is not very sensitive to the ratio of the height to the interval, but smaller values of this ratio increase the accuracy.

Interval text box

Time interval at which the repulsive Gaussian potential is added. The accuracy of the results increases as the time interval increases, but the simulation time also increases.

Temperature text box

Specify the temperature to be used, in kelvin. Not available for the NVE ensemble class.

Pressure text box

Specify the pressure to be used, in bar. Not available for the NVE and NVT ensemble classes.

Surface tension text box

Specify the surface tension to be used, in bar angstroms. Only available for the NPγT ensemble class.

Relax model system before simulation option

When selected, a series of minimizations and short molecular dynamics simulations are performed to relax the model system before performing the simulation you set up (see Relaxing a Model System). If the system contains a membrane, the option text reads Relax membrane model system before simulation, and relaxation protocols suitable for a membrane-bound system are used (see Relaxing a Membrane-Containing Model System).

Normally, this option is needed only for model systems that have just been prepared with the System Builder Panel or the Disordered System Builder Panel, and have not been relaxed. This option is selected by default for a new simulation, but is deselected and unavailable if you are starting from a checkpoint file.

Relaxation protocol text box and Browse button

Specifiy a custom protocol to be used for the relaxation. You can specify a protocol by clicking Browse and selecting the appropriate .msj file for the relaxation. The text box shows the name of the file you selected.

Advanced Options button

Opens the Metadynamics - Advanced Options dialog box, in which you can control many more of the detailed settings for the simulation than are available in the Metadynamics panel.

Job toolbar

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

The Job Settings button opens the 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.