A protein structure can look like a locked room: the atoms are there, but a binding pocket may be closed off in the conformation you are viewing. For molecular modelers, the practical challenge is not just seeing the current structure—it is exploring plausible large-scale motions that might open access, and keeping track of useful conformations along the way.
Normal Modes Advanced in SAMSON offers an interactive way to investigate this problem. Rather than moving atoms one at a time, it computes nonlinear normal modes—coordinated motions that can help explore large structural changes. The extension uses the NOLB algorithm, described by Hoffmann and Grudinin in a 2017 paper in the Journal of Chemical Theory and Computation.
Start with the structure and a focused calculation
Open a biomolecular structure in SAMSON; the tutorial uses the 1VPK PDB entry, though proteins, RNA, and DNA can be used. In the Normal Modes Advanced module, choose how many modes to compute, 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 first select a subset of residues. A focused selection can be useful when you want to inspect a region without calculating on every part of the model. Once the calculation is complete, the modes appear in the Output box.
Explore motions before settling on a target
Move a mode’s slider to display its motion on the structure. Each mode also has a checkbox and reset control. Checking multiple modes lets you combine them; use play/pause to apply the selected motions. You can still adjust unchecked sliders during motion, so pay attention to which modes are selected when interpreting the combined movement.
Several controls make exploration more flexible. You can choose linear motion (translations only) or nonlinear motion (translations and rotations), change the scaling factor to adjust motion amplitude, and modify speed. Harmonic motion can be enabled or disabled, while forward and backward step buttons let you inspect a trajectory incrementally. If desired, real-time minimization can be activated using one of the available algorithms.
This staged approach helps keep the exploration manageable: first inspect individual modes, then combine modes that move the structure in a useful direction, and adjust amplitude or motion settings as needed. Reset individual sliders or use reset all to return to zero; clear unchecks the selected modes, while update applies the slider values to the structure.
Define what “open” means for your model
When visual inspection is not enough, the Structure Definition tab lets you define a target structure and find a combination of modes that reaches it. A definition can contain residues or atoms, which gives you a way to express the region or structural change you want to examine.
For a pocket-opening task, the useful question is therefore not simply “Which mode is largest?” Instead, define the structural target that matters, then explore the mode combination that moves toward it. Treat the resulting motion as a way to investigate conformational possibilities, not as a substitute for deciding whether a conformation is biologically relevant.
Keep the useful states
Once you find a conformation worth revisiting, save it as a SAMSON conformation with the S shortcut. To compare or superpose structural states, create a structural model instead; the module also offers export of the current structure as a PDB file. For a sequence of states, set a saving interval in the Save Frames tab and store conformations or export PDB files. The Path button can store the full trajectory in a SAMSON trajectory node.
Before saving a trajectory, check the settings that determine it: selected modes, their slider values, scaling factor, motion type, and saving interval. Keeping these settings in mind makes it easier to understand what the saved frames represent when you return to them later.
For the complete workflow and additional controls, see the Normal Modes Advanced tutorial.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at samson-connect.net.