A molecular structure can show a binding site that looks closed, even when a nearby conformation might make it accessible. The challenge is that a static structure captures one arrangement of atoms—not the range of motions the molecule may undergo. For modelers, the next question is often practical: which collective movements could open the pocket, and how can those movements be explored without manually dragging parts of the structure?
SAMSON’s Normal Modes Advanced extension provides a way to investigate that question through nonlinear normal modes. It uses the NOLB algorithm to calculate large-scale motions in proteins, RNA, and DNA. These modes are useful for exploring possible structural changes; they should be treated as a way to inspect candidate motions, not as proof that a particular conformation occurs biologically.
Start with a structure and a focused calculation
Open a biomolecular structure in SAMSON, such as the 1VPK example used in the tutorial, then launch Normal Modes Advanced. Choose the number of modes, the interaction cutoff distance, and the potential function. The interface currently offers the elastic network model potential. You can calculate modes for the full structure or select a subset of residues first using SAMSON’s selection tools.
A useful way to keep the exploration manageable is to begin with the region relevant to the question. If the pocket is formed by a particular group of residues, selecting that subset can focus the calculation. If you need to understand how local movement relates to the rest of the molecule, calculate on the full structure instead. In either case, note what was selected and which calculation settings you used so you can interpret the resulting motion in context.
Inspect modes before combining them
After the calculation, the Output box displays the modes. Moving a mode’s slider shows its motion on the structure. This gives you a way to examine individual movements before deciding which ones might contribute to opening or closing the site.
Pay attention to which parts of the structure move together and whether a mode changes the geometry around the pocket. The sliders can be reset individually, making it easier to return to a neutral starting point and compare another mode. A mode that moves the pocket-forming region may be worth exploring, but visual inspection alone does not establish that the motion is energetically or biologically likely.
Combine motions to explore a pocket objective
Once you have inspected individual modes, check the modes you want to combine and use play/pause to apply their motions together. Sliders can also be adjusted while motion is running, so the displayed trajectory reflects those changes. You can choose linear motion, which applies translations only, or nonlinear motion, which includes translations and rotations. The scaling factor changes the motion amplitude; motion speed and harmonic behavior can also be adjusted.
For a more specific objective, use the Structure Definition tab. The target definition can contain residues or atoms, and the module can find a combination of modes that reaches the defined target structure. This is a practical way to turn “I want to see whether this pocket can open” into a concrete structural comparison. Real-time minimization is also available during motion, with three minimization algorithms in the interface. Use it as part of exploration, and inspect the resulting structure rather than assuming minimization makes a conformation experimentally validated.
Keep useful conformations and trajectories
When you find a conformation worth revisiting, save it as a SAMSON conformation using the S shortcut. To compare structural states by superposing them, create a SAMSON structural model instead; you can also export the current structure as a PDB file. If the path itself matters, the Save Frames tab can store sampled conformations or export frames as PDB files. The Path button stores the trajectory in a SAMSON trajectory node.
Before saving, check the settings in the Calculations tab. The saved trajectory and conformations reflect the checked modes, their slider values, the scaling factor, the motion type, and the saving interval. Keeping these settings in mind makes it easier to reproduce or interpret a result later.
Nonlinear normal modes are most useful here as an interactive way to explore structural possibilities: inspect individual motions, combine promising modes, define a target, and preserve the conformations that help answer your modeling question. For the full walkthrough, see the original documentation page.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.