A molecular structure can show where a binding site is, but a single structure does not tell you how that site might open, close, or connect to another conformation. For modelers, this creates a familiar frustration: the pocket looks inaccessible in the current model, and it is not obvious which collective motion could create useful space.
One practical way to investigate is to explore nonlinear normal modes. In SAMSON, the Normal Modes Advanced extension uses the NOLB algorithm to compute modes for biomolecular systems such as proteins, RNA, and DNA. Rather than treating every atom’s movement as an isolated change, the modes provide motions you can inspect and combine while watching the structure respond.
Start with a structure and a focused question
Open a biomolecular structure in SAMSON; the tutorial uses the 1VPK PDB entry, though you can use your own model. Add and launch the Normal Modes Advanced extension. Before computing, decide whether you want to explore the whole structure or focus on a subset of residues. SAMSON selection tools let you select residues before starting the calculation.
Set the number of modes, the interaction cutoff distance, and the potential function. The interface currently provides the elastic network model potential. Once the calculation finishes, its results appear in the Output box. You can then move individual mode sliders and immediately see the corresponding motion. This makes it easier to compare modes visually instead of guessing from a static structure.
Build a motion deliberately
Not every mode will help answer the same structural question. Inspect modes one at a time, noting which parts of the molecule move and whether the motion changes the region you care about. Each mode has a slider, checkbox, and reset control. Check the modes you want to combine, then use play to apply their motion. You can still adjust unchecked sliders during playback, so the displayed trajectory can reflect those manual changes too.
For a pocket-opening objective, define the relevant residues or atoms in the Structure Definition tab. You can specify a target structure and find a combination of modes intended to reach it. The images below show the pocket-definition and target-structure workflows.
As you explore, use the motion controls to compare alternatives. The transformation can be linear, using translations only, or nonlinear, using translations and rotations. Adjust the scaling factor to change motion amplitude, and change the speed or harmonic setting to inspect the trajectory at a useful pace. Forward and backward step controls let you examine changes incrementally. Real-time minimization is also available during motion, with a choice of three minimization algorithms.
Keep the result you can use
When you find a conformation worth revisiting, save it rather than relying on memory. You can store a conformation in the document with the S shortcut, create a SAMSON structural model, or export the current structure as a PDB file. To preserve a trajectory, use the Save frames tab: set a saving interval, then store conformations or export PDB files. The Path button can save the trajectory as a SAMSON trajectory node.
Remember that saved conformations and trajectories use the current calculation settings, including checked modes, their slider values, the scaling factor, motion type, and saving interval. Before saving, take a moment to confirm those settings match the motion you intend to keep.
Normal-mode exploration is a way to investigate plausible structural movement and generate conformations for further analysis; it does not, by itself, establish that a pocket will open under experimental conditions. For the full workflow and controls, read the original SAMSON documentation tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON.