A protein structure can make a binding site look smaller—or less accessible—than you expect. The challenge is that a static model shows one conformation, while proteins can undergo larger motions that change the shape of a pocket. Instead of judging accessibility from a single structure, you can explore candidate motions with nonlinear normal modes in SAMSON.
The Normal Modes Advanced extension computes nonlinear normal modes for biomolecular systems such as proteins, RNA, and DNA using the NOLB algorithm. The modes provide a way to interactively explore large-scale movements, including motions that may open or close a defined pocket. They are useful for investigating possible conformations; they do not, by themselves, establish that a particular motion occurs under biological or experimental conditions.
Start with a structure and a focused question
Open a biomolecular structure in SAMSON before launching the extension. The tutorial uses the PDB structure 1VPK, though you can use your own protein, RNA, or DNA model. It helps to decide what you want to inspect before calculating: the movement of the whole structure, a particular region, or the opening of a pocket.
In the NMA module, choose the number of modes, the interaction cutoff distance, and the potential function. The interface currently provides 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 focused selection can make the analysis more relevant when your question concerns a particular part of the molecule.
Explore modes without losing the structural context
After the computation, the modes appear in the Output box. Move a mode’s slider to see its motion on the structure. This is a practical first pass: compare the motions rather than assuming that the first one you inspect is the one relevant to your question.
Each mode has a checkbox and a reset button. Check modes to combine them, then use play/pause to apply the selected motions. The sliders for unchecked modes can still be adjusted during playback, so keep track of which modes are selected when interpreting the resulting movement. Use reset to return individual sliders to zero, or reset all to clear their values; the clear button unchecks the modes, while update applies the current slider values to the structure.
The transformation can be linear, using translations only, or nonlinear, using translations and rotations. A scaling factor changes the amplitude of the motion. These controls are useful for inspecting a movement at different magnitudes, but a visually open pocket is best treated as a candidate conformation to examine—not as a conclusion about binding or accessibility.
You can also activate real-time minimization while modes are applied, choosing among the available minimization algorithms. Motion speed, harmonic playback, and forward or backward trajectory steps are additional controls for inspecting how the structure changes over time.
Define the pocket or target explicitly
For a more directed exploration, use the Structure Definition tab. The definition can include residues or atoms, and you can specify a target structure. The module can then find a combination of modes intended to reach that target. This shifts the task from browsing motions one by one to asking a more specific question: which combination of available modes moves the selected structure toward the defined target?
For pocket exploration, this is a useful way to organize the analysis: define the region or target you care about, inspect the suggested mode combination, and review the resulting structure in context. The goal is not simply to produce a dramatic animation, but to identify conformations worth retaining for comparison or further study.
Keep the conformations you want to revisit
When you find an interesting state, save it as a SAMSON conformation with the S shortcut. Conformations let you restore saved states, while a structural model is the better choice when you want to superpose multiple states. You can also export the current structure as a PDB file.
To preserve motion over time, use the module’s save frames tab to store sampled conformations or export trajectory frames as PDB files. The Path button stores the trajectory in a SAMSON trajectory node. Before saving, check the calculation settings: the saved trajectory reflects the checked modes, their slider values, the scaling factor, motion type, and saving interval.
This workflow turns a static pocket question into a sequence of inspectable steps: calculate modes, compare motions, define a target when useful, and save conformations that merit follow-up. For the full walkthrough and interface details, see the Normal Modes Advanced tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.