Compute normal modes that open a binding site#

Use the Normal Modes Advanced (NMA) extension when you want to explore large-scale biomolecular motions, such as opening a binding site or connecting two nearby conformations. It extends the Normal Modes Analysis extension with richer controls for nonlinear motion analysis in SAMSON.

This extension computes nonlinear normal modes of a biomolecular system (protein, RNA, DNA) using the NOLB algorithm developed by Alexandre Hoffmann and Sergei Grudinin (J. Chem. Theory Comput., 2017, 13 (5), pp 2123-2134).

Before you start#

Add Normal Modes Advanced from SAMSON Connect - Marketplace.
Open a biomolecular structure in SAMSON before launching the extension. The examples on this page use the 1VPK PDB entry.
Use this page when you want to explore motions interactively, define a target opening/closing objective, or save interesting conformations for later work.

Compute and explore the modes#

Start by importing a structure. This tutorial uses 1VPK, but you can use your own protein, RNA, or DNA model.

Then launch the NMA module and choose the main calculation settings:

the number of modes to compute
the interaction cutoff distance
the potential function to use

At the moment, the elastic network model potential is the one available in the interface. You can run the calculation on the full structure or only on a selected subset of residues by using SAMSON's selection tools before starting the computation.

During computation, a progress bar is displayed and the computation steps are shown in the SAMSON status bar. A few seconds later, the result of the computations is displayed in the Output box:

Computing normal modes for selected residues

Moving a slider will instantaneously display the mode-specific motion of the structure:

Going through specific modes

Note how each mode also has a specific checkbox and reset button. Modes can be combined (when their checkbox is checked) and applied to the structure using the play/pause button. Note that, during motion, the unchecked sliders can still be manually modified. Therefore, the motion obtained from this modification will also be displayed during the trajectory:

Applying only certain modes

While the mode motions are applied to the structure, real-time minimization can be activated, using one of three available minimization algorithms:

Applying real-time minimization

Mode sliders can be reset to zero either independently using their corresponding reset button or all simultaneously using the reset all button. Also, all checked modes can be unchecked using the clear button, while the update button applies the values of the sliders to the structure:

Going through modes

During motion, the type of transformation applied can be either linear (translations only) or nonlinear (translations and rotations). And the scaling factor can be increased or decreased to change the amplitudes of the motion:

Changing the amplitude of the motion

The motion speed can be modified while the motion type can be harmonic or not. Forward and backward steps buttons can be used to navigate through the trajectory step by step:

Changing the motion speed and navigating through the motion trajectory

Structure definition#

In the Normal Modes Advanced module, you can find the best combination of normal modes that can open/close a defined pocket. This definition can contain residues or atoms.

Finding normal modes that open/close a defined pocket

In the Structure Definition tab, you can define a target structure and find the best combination of modes that will reach this target structure.

Finding normal modes that will reach the target structure

Save/export a resulting conformation#

When an interesting conformation of the structure is found, you can save it in different ways.

First, you can store a conformation of the structure in the document (shortcut S). With SAMSON conformations you can quickly restore the saved conformation of the structure:

Saving a conformation

However, using SAMSON conformations, you will not be able to superpose several states of the structure. For this kind of operation, you need to create a SAMSON structural model. To do that, select the entire structure, or only part of it, then click on the create button of the NMAL app. You can also export the current structure as a PDB file using the export button:

Creating structures

You can store the entire trajectory by going to the save frames tab of the module. Once the saving interval has been set, you can either store the trajectory as a set of conformations by clicking on the store button or export the trajectory as PDB files using the export button. By double-clicking on the conformation node, you can directly display it. Also, the SAMSON conformations that represent the trajectory can be removed using the remove button:

Creating conformations along the trajectory

It is also possible, by clicking on the Path button, to store the entire trajectory in the new SAMSON trajectory node. You can start and pause the playing of the trajectory by double-clicking on the trajectory node.

Creating the trajectory

Finally, note that the trajectory and the conformations will be saved using the current settings of the calculations tab. These settings include the motions corresponding to the checked modes, the current slider value of the checked modes, the value of the scaling factor, the motion type (harmonic or not), and, of course, the saving interval.

Need Help?#

Have questions or feedback? Feel free to reach out via the Forum, via e-mail, via the Feedback button in SAMSON, or by directly discussing with us.