System Builder Panel

The System Builder panel allows you to set up a system consisting of proteins, ligands, explicit solvent, membrane, and counter ions, so that you can perform simulations on the system with Desmond. The solutes (proteins, ligands) must be placed in the Workspace

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

  • Using
  • Features
  • Additional Resources

Using the System Builder Panel

Performing simulations on aqueous biological systems requires preparation of biological molecules such as proteins and ligands, addition of counter ions to neutralize the system, selection of simulation box size, solvation of the solutes using explicit solvent molecules, and alignment of proteins to a membrane bilayer (if used). This procedure is often tedious and needs much manual work. It is even more difficult to add counter ions in certain positions to avoid their artificial interference on the actives sites of interest. The System Builder automates this process and significantly reduces the effort required. Once the solute biological molecules are prepared, the System Builder performs these other tasks.

Preparation of proteins should be performed with the Protein Preparation Workflow Panel. Preparation of ligands or other small molecules should be performed with LigPrep.

System builder jobs can be run on Linux, Mac, and Windows platforms, unlike the simulation jobs based on Desmond, which can only be run on a GPU on Linux.

If you want to run the job from the command line, click the arrow next to the Settings button and choose Write. The Write dialog box opens, in which you can specify a name and then write the file. The name is equivalent to a job name, and is used to construct the file names by adding the appropriate extension.

The instructions below take you through the simplest setup procedures. Before you use them, ensure that you have imported the protein and ligand structures into Maestro, and displayed them in the Workspace.

To set up the solvent:

  1. Select Predefined for the Solvent model option, and choose a model from the option menu.
  2. Choose the box shape.
  3. Select a box size calculation method.
  4. Enter buffer distances or side lengths in the available text boxes.
  5. Enter angles if you selected Triclinic for the box shape.
  6. If you want the minimum box volume, click Minimize Volume.

To add ions:

  1. In the Ions tab, choose an option for the addition of ions.
  2. If you selected Add, enter the number of ions to add in the text box.
  3. Choose an ion type from the option menu.
  4. If the solvent is intended to be a salt solution, select Add salt.
  5. Enter the desired salt concentration in the Salt concentration text box.
  6. Choose positive and negative ion types from the Salt positive ion and Salt negative ion option menus,

To add a membrane:

  1. Click Set Up Membrane in the Solvation tab.
  2. In the Desmond - Set Up Membrane panel, select Predefined for the membrane model, and choose a membrane type from the option menu.
  3. Click Position Membrane.
  4. Select Adjust membrane position and adjust the orientation of the solutes in the Workspace.
  5. Click OK.

When you have finished making all the desired settings, choose Job Settings from the Settings button menu,

set the job parameters in the Job Settings dialog box, and click Run to run the job.

The resulting model system can be added to the project as a new entry if you choose Append new entries. Otherwise, the model system is written to your working directory.

Note that alternate coordinates are deleted when the system is built.

To edit and rebuild a model system:

  1. Display the entry for the full model system in the Workspace.

  2. Make the desired changes to the entry.

  3. Click the Tasks button and browse to Classical Simulation → Model System Regeneration.

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.

System Builder Panel Features

Solvation tab

In this tab you set up the solvent and the membrane, and define the box used for the periodic boundary conditions. The solvent is placed by replicating “boxes” of solvent molecules and deleting molecules whose center of mass lies outside the periodic box boundary, and molecules that are inside or have significant overlap with the solute or the membrane (if one is used).

Set Up Membrane button

Opens the Desmond - Set Up Membrane dialog box, in which you can set up a membrane.

Delete Membrane button

Delete the membrane from the system, if one has been defined.

Solvent model options

Specify the solvent to use. You can choose from a set of predefined solvent models, or provide a custom solvent model.

  • None—Do not use a solvent. This allows you to run simulations for a pure liquid, for example, or in vacuum (low-density gas).
  • Predefined—Use one of the predefined solvent models, which you can select from the option menu. The available models are six water models, SPC, TIP3P, TIP4P, TIP4PEW, TIP5P, and TIP4PD, and three organic solvents, DMSO, METHANOL, and OCTANOL.
  • Custom—Import a custom solvent system from file. Enter the solvent system file name in the text box, or click Browse, and navigate to the solvent system file in the file selector that is displayed. For information on creating a custom solvent, see Preparing a Custom Solvent Box.
Boundary conditions section

In this section you set up the parameters of the periodic box used for the simulation.

Box shape option menu

Select the box shape. Three basic shapes are provided: Cubic, Orthorhombic, and Triclinic. As special cases of the triclinic box shape, three other shapes are supported: Truncated octahedron, Rhombic dodecahedron xy-square, and Rhombic dodecahedron xy-hexagon. The default shape is orthorhombic.

Box size calculation method options

Specify the box boundary either in terms of a buffer region around the solute or a specified size.

  • Buffer—The simulation box size is calculated by using the given buffer distance between the solute structures and the simulation box boundary.
  • Absolute size—Specify the lengths of the sides of the simulation box size (and angles if necessary).
Distances or Size text boxes

Set the buffer distances or side lengths, in angstroms, in these text boxes. The label depends on the choice of boundary condition. The available text boxes depend on the box shape. For the Cubic, Truncated octahedron, Rhombic dodecahedron xy-square, and Rhombic dodecahedron xy-hexagon box shapes, only the text box for the a axis is available.

Angles text boxes

Specify the alpha, beta, and gamma angles for the box. This option is only active if you selected Triclinic box shape.

Box volume text box

This noneditable text box displays the volume of the boundary box.

Minimize Volume button

Find the orientation of the solutes that has the minimum box volume, and reorient the solutes.

Show boundary box option

Select this option to display the boundary box for the solvent. Available for all except truncated octahedron box shapes.

Use custom charges section

Enable the use of custom partial atomic charges for selected atoms, rather than the partial charges supplied with the force field. Selecting this option activates the controls in this section.

Charge source options
  • Do not use—Select this option to use the standard charges from the force field.
  • Partial charges from structure—Use the partial charges in the input structure.
  • Custom—Use the property name given in the text box to define the custom charges. The property name is the internal name, which should start with r_. For example, the property r_j_ESP_Charges selects Jaguar-generated ESP charges. See Property Names for more information on the internal names.
Apply to text box and Select button

This text box specifies the ASL expression for the atoms for which custom charges are to be used. There is no default. Click Select to open the Atom Selection Dialog Box and select the atoms to use. For a property where only the relevant atoms have values, you can enter the entire range of values (which is displayed in the center of the tab) to select those atoms. Atoms that do not have a value for the property are not selected.

Ions tab

It is usually desirable to have an electrically neutral system for simulation (though not strictly necessary). In this tab you select ions to use for counter ions and as a salt solution, and add these ions to the system. This tab has three sections: Excluded region, Ion placement, and Add salt.

Excluded region section

In this section you define a region in which ions (both counter ions and salts) will not be placed. The region is defined in terms of a buffer zone around an atom selection.

Exclude ion and salt placement within text box

In this text box, enter the distance from the selected atoms that define the region from which ions will be excluded.

Select button

Click Select to select the atoms that will be used to define the exclusion region. Opens the Atom Selection Dialog Box so that you can select the atoms. The ASL expression for the atom selection is displayed in the noneditable text box to the left. The selected atoms are colored blue and rendered in CPK in the Workspace.

Clear button

Click Clear to clear the ASL expression for the selected atoms.

Ion placement section

In this section, you can set up the placement of ions. Automatic placement is done by selecting one of the options for adding counter ions; manual placement is done in the Advanced ion placement dialog box. When the job is run, manual placement of ions is done before automatic placement. Once these ions are placed, random placement is performed to place any remaining ions that are needed to neutralize the system or complete the number of ions selected for placement in the Add text box.

Ion placement options

Select one of these options for ion placement.

  • None—Do not add counter ions.
  • Neutralize by adding—Neutralize the net charge of the system automatically by adding ions. You can choose the ion type from the option menu. The number of ions is given to the left of the option menu. Click Recalculate to recalculate the number of ions. Neutralization is done after manual placement of ions.
  • Add—Enter the number of ions to add in the text box and choose the ion type from the option menu. This number includes any manually placed ions; the remainder (if any) are automatically placed.
Advanced ion placement button

Opens the Advanced Ion Placement Dialog Box, in which you can control where the ions are placed. Automatic ion placement is done after placement of ions using this dialog box.

Add salt option and section

Select this option to add salt to the solution. The controls below are activated.

Salt concentration text box

Enter the salt concentration in mol dm-3. This value is used to calculate the number of ions in the system. For example, for MgCl2 the concentration of Mg2+ would be the specified concentration and the concentration of Cl− would be twice the specified concentration. A value of 0.15M is approximately the physiological concentration of monovalent ions.

Salt positive ion and Salt negative ion option menus

Choose positive and negative ions from these option menus to define the salt to be used to convert the pure solvent to a salt solution.

Force field option menu

Choose the force field for the simulations. The choices are OPLS_2005, OPLS4, and OPLS5. The default is OPLS4 if it is available, otherwise it is OPLS_2005, unless you set the default in the Force Field settings section of the Preferences Panel.

Use customized version option

Use your customized version of the OPLS4 or OPLS5 force field, rather than the standard version in the distribution. Only available when you choose OPLS4 or OPLS5 from the Force field option menu and you have the appropriate license. This option is set by default to the value of the Use custom parameters by default option in the Preferences panel, under Jobs - Force field, when the current panel is opened. The default directory for the customized version can also be specified as a preference, in the same location.

If the customized version is missing or invalid, the text of this option turns orange and an orange warning icon is displayed to the right, with a tooltip about the problem.

Parameter set button

Select the set of custom parameters for the OPLS4 or OPLS5 force field. Opens the Set Custom Parameters Location Dialog Box. Only available when you choose OPLS4 or OPLS5 from the Force field option menu and you have the appropriate license.

Note: The custom force field used in the simulations is located at the path specified in the Force Field settings section of the Preferences Panel that is current when the simulation is run. This path could be different from the one that is current when the system is built, if you change the path after building the system. This applies also to systems prepared with a custom force field prior to the 2020-3 release, where the force field location was stored in the CMS file. Simulations run with these systems use the current custom force field, not the one specified in the CMS file.

Job toolbar

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

The Job Settings button opens the System Builder - 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.

Tutorials

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