One of the recurring challenges faced by molecular modelers is identifying and triggering functionally relevant conformational changes in biomolecules—such as the opening of a binding pocket—without resorting to computationally intensive simulations. Normal mode analysis (NMA) offers a far more efficient alternative, and with the Normal Modes Advanced extension in SAMSON, it’s now easier than ever to selectively open or close specific molecular regions.
This blog post focuses on the Structure Definition feature of the Normal Modes Advanced module. This tool allows you to define a molecular region—residues or atoms—that you want to open (or close), and then compute the optimal combination of non-linear normal modes to achieve that structural change. All of this happens in a faster and more interactive way than traditional molecular dynamics simulations.
What problem does this solve?
Let’s say you’re analyzing a protein with a ligand-binding site that’s partially occluded in the crystal structure. You want to model how this site can open up to accommodate a drug molecule, but traditional MD simulations may take days to sample such large conformational changes, if they reach them at all.
With SAMSON’s NMA module, you define the pocket you want to open by selecting relevant residues or atoms. From there, the module computes and applies the optimal set of non-linear normal modes—collective movements derived from the molecule’s internal flexibility—that direct the structure toward the desired conformation.
How does it work in practice?
In the Structure Definition tab of the NMA module, you can:
- Select the pocket or region of interest using filters (individual atoms or residues).
- Mark this as the target whose geometry you wish to achieve by moving the structure.
- Let the module search for a combination of normal modes that best drives your structure toward this target state.
As shown in the example below, this process is fully visual: mode contributions are computed and applied dynamically, allowing the user to immediately observe the structural transformation.
Once the movement opens the desired pocket, you can:
- Store the conformation inside your SAMSON document using the S shortcut.
- Apply minimization options for energy refinement.
- Export the resulting structure as a PDB for further analysis or docking experiments.
Why it matters
This targeted NMA approach provides a way to explore biologically meaningful conformations with minimal manual tweaking or brute-force computation. Whether you’re modeling allosteric transitions or preparing receptor structures for docking, it gives you greater control over structural sampling.
And importantly, it avoids overfitting or non-physical transformations. Since the modes themselves are derived from the molecule’s structure and energetics (via the NOLB algorithm), they remain physically relevant while providing structural flexibility.
Wrapping up
The Structure Definition capability in SAMSON’s Normal Modes Advanced extension is a practical and time-saving tool for molecular modelers needing to open, close, or shift molecular regions with control and efficiency. You can test different hypotheses, explore potential intermediate states, and prepare structures for docking—all within a few clicks.
To learn more about this feature and other capabilities of the NMA module, visit the complete tutorial page: https://documentation.samson-connect.net/tutorials/nma/calculating-non-linear-normal-modes/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.