A protein structure can look like a locked door: the binding pocket you want to study is too narrow, partly hidden, or positioned differently from the conformation you need. The practical challenge is not just seeing that the site is closed—it is exploring plausible large-scale motions without manually dragging parts of the molecule and losing track of what changed.
SAMSON’s Normal Modes Advanced extension offers a way to explore such motions using nonlinear normal modes. The NOLB algorithm computes modes for biomolecular systems, and the interface lets you inspect individual modes, combine them, adjust their amplitudes, and define a target structure. This makes it possible to investigate how a structure might move toward an open or closed pocket, then save conformations that are useful for later work.
Start with a structure and a focused question
Open a protein, RNA, or DNA structure in SAMSON. The tutorial uses the 1VPK PDB entry, but you can use another structure. Before calculating, decide whether you want to explore the whole molecule or focus on a particular region. You can select residues with SAMSON’s selection tools and calculate on that subset.
In the NMA module, choose the number of modes, interaction cutoff distance, and potential. The documented interface currently provides the elastic network model potential. After calculation, the results appear in the Output box.
Read the motion before combining modes
Move a mode’s slider to display its motion on the structure. Treat this as a way to inspect possible coordinated movements: a mode may suggest which regions move together, or whether a motion is relevant to the pocket you are trying to open. The aim is to explore and compare structural changes, not to infer a binding event from a single slider movement.
When you have identified modes worth testing, check their boxes and use play to apply them together. You can still adjust unchecked sliders during motion, so keep track of which modes are selected when interpreting the resulting trajectory. Reset a single mode with its reset button, reset all slider values at once, or use Clear to uncheck all modes. Update applies the current slider values to the structure.
Adjust the motion without losing your reference point
The interface allows you to choose linear motion (translations only) or nonlinear motion (translations and rotations), and to change the scaling factor to adjust motion amplitude. Motion speed and whether the motion is harmonic can also be changed. Forward and backward step controls let you inspect the trajectory incrementally instead of relying only on continuous playback.
Real-time minimization can also be activated while modes are applied, using one of the available minimization algorithms. If you use minimization, compare the resulting structure with the unminimized motion: the two settings answer different exploratory questions. Keep the starting structure available so that you can judge changes against the original rather than memory.
Turn a pocket-opening question into a target
If you have a specific desired arrangement, use the Structure Definition tab to define a target structure. The definition can contain residues or atoms, and the extension can search for a combination of modes that reaches the target. This is useful when “open the pocket” can be expressed as a concrete structural objective—for example, a target arrangement of selected atoms or residues—rather than judged only by watching the animation.
Save the result in the form you will need later
For a single interesting state, save a SAMSON conformation (shortcut S) so you can restore it in the document. If you need to superpose multiple states, create a SAMSON structural model instead; you can select the whole structure or a subset, then use the app’s Create button. The current structure can also be exported as a PDB file.
For a series of states, configure the saving interval in the Save frames tab and store frames as conformations or export them as PDB files. To retain the complete motion as a trajectory node, use the Path button. Before saving, check the calculation settings: the resulting conformations and trajectory use the checked modes, their slider values, the scaling factor, motion type, and saving interval. Recording these settings alongside your chosen structure makes the result easier to interpret and revisit.
The key is to work in stages: inspect modes, combine only those relevant to your question, define a target when you have one, and save the output in the format that supports your next step. For the full workflow and interface details, read the Normal Modes Advanced tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at samson-connect.net.