A binding pocket can look accessible in one structure and closed in another. If you are modeling a protein, RNA, or DNA, the challenge is not just to see the atoms in their starting positions—it is to explore plausible large-scale motions that might open the site. Manually dragging parts of a molecule can be hard to interpret, while a static structure alone does not show how its shape may change.
SAMSON’s Normal Modes Advanced extension offers a way to explore these motions using nonlinear normal modes. Rather than treating each atom as moving independently, the method helps you inspect coordinated changes in the biomolecular structure. The goal is practical: find modes, or combinations of modes, that move the structure toward a pocket-opening objective, then save useful conformations for further analysis.
Start with a structure and a focused calculation
Open a biomolecular structure in SAMSON before launching the extension. The tutorial uses the PDB entry 1VPK, but you can work with your own protein, RNA, or DNA model. In the NMA module, choose the number of modes, interaction cutoff distance, and potential function. The interface currently provides the elastic network model potential.
You can calculate modes for the full structure or first select a subset of residues using SAMSON’s selection tools. A focused selection can be useful when you want to examine a particular region, but keep in mind that the chosen subset defines what is included in that calculation.
Once the calculation is complete, the output lists the modes. Moving a mode’s slider displays its corresponding motion on the structure. This gives you a quick way to inspect whether a mode changes the region around the binding site in a potentially useful direction.
Combine motion without losing control
A pocket may not open through a single mode. In the interface, each mode has a checkbox, slider, and reset button. Check the modes you want to combine, then use play to apply the selected motion. You can adjust slider values while the motion is running; unchecked modes can also be modified manually, and those changes are displayed during the trajectory.
This makes exploration more deliberate than simply watching a single animation: you can test how selected modes contribute to the shape change, reset an individual mode, or reset all sliders. Use clear to uncheck the selected modes, and update to apply the current slider values to the structure.
The motion can be set to linear, using translations only, or nonlinear, using translations and rotations. A scaling factor changes the motion amplitude. These controls are useful for visual exploration, but a visually open pocket should be treated as a candidate conformation to investigate—not, by itself, proof that the structure adopts that state biologically.
Define the opening you want to explore
When you have a specific objective, use the Structure Definition tab. The definition can include residues or atoms. You can define a target structure and ask the module to find a combination of modes that reaches it. This shifts the question from “Which motion looks interesting?” to “Which combination moves the structure toward this specified target?”
Real-time minimization can also be activated while applying mode motions, using one of the available minimization algorithms. If you use it, compare the resulting structures and keep track of the settings: the selected modes, slider values, scaling factor, motion type, and minimization choice all affect what you see.
Keep the conformations you may need later
When you find a useful state, save it rather than relying on a remembered slider position. Press S to store a conformation in the document for quick restoration. To superpose multiple states, create a SAMSON structural model from the whole structure or a selected part; you can also export the current structure as a PDB file.
For a sequence of states, use the save frames tab to store conformations at a chosen saving interval or export frames as PDB files. The Path button stores the trajectory in a SAMSON trajectory node. Remember that saved trajectories and conformations use the current calculation settings, including the checked modes and their slider values. Recording those choices makes later comparisons easier to interpret.
This workflow helps turn an abstract flexibility question into a set of inspectable structures: calculate modes, explore combinations, define a target when you have one, and preserve the states that merit follow-up. For the complete interface walkthrough, see the Normal Modes Advanced tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.