A protein structure is a snapshot, but a binding site may open only as the molecule moves. That creates a familiar problem for molecular modelers: the pocket is difficult to assess from one conformation, and it is not obvious which parts of the structure need to move to expose it. Nonlinear normal modes in SAMSON offer a way to explore larger-scale motions and identify conformations worth examining—without treating a single static structure as the whole story.
The Normal Modes Advanced extension computes nonlinear normal modes for biomolecular systems such as proteins, RNA, and DNA using the NOLB algorithm. In the interface, you can calculate modes for the full structure or first select a subset of residues. This can be useful when your question concerns a particular region, although the choice of what to select depends on the system and the motion you want to inspect.
Start with a structure and a focused question
Open a biomolecular structure in SAMSON; the tutorial uses the PDB entry 1VPK. Before calculating, decide whether you want to inspect general motions or focus on a region relevant to the binding site. The calculation settings include the number of modes, interaction cutoff distance, and potential function. The interface currently provides the elastic network model potential.
Once the calculation finishes, its results appear in the Output box. Each mode has a slider, so you can inspect its motion individually. This is a helpful first pass: move through the modes and watch how different regions respond instead of immediately combining everything into one trajectory.
Build and assess a motion
When you find modes worth exploring, check them to combine their contributions and use the play/pause control to apply the motion. Checked modes participate in the applied motion; unchecked sliders can still be adjusted manually, and those changes are also displayed during the trajectory. You can reset a single slider or reset all of them, clear the checked modes, or update the structure using the current slider values.
Motion settings help you inspect the result in different ways. You can choose linear transformations (translations only) or nonlinear transformations (translations and rotations), adjust the scaling factor to change motion amplitude, and modify the speed. Motion can be harmonic or non-harmonic, and forward/backward step controls let you move through a trajectory one step at a time. Real-time minimization can also be enabled during motion, using one of the available minimization algorithms.
These controls are useful for exploration, but the animation itself is not the final answer to a structural question. Pay attention to which regions move and whether the resulting conformation is useful for the specific pocket or target you are investigating. If you have a target structure in mind, the Structure Definition tab lets you define it using residues or atoms and find a combination of modes that reaches that target.
Keep the conformations you want to revisit
Once you find an interesting state, save it in a form that fits your next step. A SAMSON conformation, saved with the S shortcut, makes it quick to restore a structure state. If you need to superpose multiple states, create a SAMSON structural model instead; you can select the entire structure or just part of it and use the module’s create button. The current structure can also be exported as a PDB file.
For a series of states, use the save frames tab and set a saving interval. You can store frames as conformations or export them as PDB files. Alternatively, the Path button stores the trajectory in a SAMSON trajectory node, which can be played by double-clicking it. Remember that saved trajectories and conformations reflect the current calculation settings, including checked modes, their slider values, scaling factor, motion type, and saving interval.
This workflow turns a vague question—“could this pocket open?”—into a sequence you can inspect and preserve: calculate modes, explore combinations, compare against a target if you have one, then save the conformations or trajectory that are useful for further analysis.
For the full tutorial and interface details, read the Normal Modes Advanced documentation.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.