Controlling the conformation of a biomolecule to open or close a binding site is often a challenging step in molecular modeling. Whether you’re setting up a drug docking simulation or analyzing conformational flexibility, being able to guide molecular motion toward a specific structural state can save hours of trial-and-error. The Normal Modes Advanced extension in SAMSON helps address this challenge with a useful feature: structure-targeted normal mode combination.
This blog post outlines how to use the Structure Definition feature in Normal Modes Advanced to explore conformational changes—especially to open or close a molecular pocket—using computed nonlinear normal modes.
Why this matters
Many molecular modeling tasks begin with a static structure that doesn’t clearly show an open or accessible binding site. Opening a hidden or collapsed site often requires simulating realistic movement of atoms—but traditional molecular dynamics simulations can be time-consuming and complex to interpret. Instead, computing normal modes offers a simplified way to estimate likely conformational changes.
With the Structure Definition tab in the Normal Modes Advanced module, you can interactively define a target structure—e.g., one with an open pocket—and use the software to find the best combination of normal modes that transforms the original conformation toward that target. The ease of integration and visualization built into the SAMSON interface makes this process fast and interactive.
How it works
Start by importing your biomolecular structure, such as a PDB file (e.g., 1VPK). Launch the Normal Modes Advanced extension, go to the Structure Definition tab, and define the part of the molecule that you want to open or close—this could be a group of residues or atoms near a binding site.
Next, provide a target structure that represents the desired conformation: an opened pocket, a different alignment, or simply a slight spatial adjustment. SAMSON will help determine which combination of nonlinear normal modes and associated amplitudes can best transform the molecule from its original shape to the targeted one.
The output is a visual transformation pathway that can be played and adjusted interactively. You can inspect which modes are responsible for specific motions and combine them in different ways to fine-tune the changes. This is especially useful when you’re experimenting with alternative ligand access pathways or testing hypotheses about motion-driven mechanisms.
As a further step, users can apply trajectory recording or export the final conformational state as a PDB file for later use. This makes it easy to integrate the modified structure into follow-up workflows, such as docking, energy minimization, or further analysis.
Recap of the process
- Load your molecular structure into SAMSON.
- Open the Normal Modes Advanced extension.
- Navigate to the Structure Definition tab.
- Select the pocket or region of interest.
- Define or import a target structure.
- Compute the combination of modes that leads to the desired conformation.
- Inspect and modify the results interactively.
- Export or save your results for further use.
If you’ve ever wanted to refine a docking pocket, open a cryptic binding site, or visualize the intrinsic structural flexibility of a molecule, this feature could make your workflow more efficient and more intuitive.
You can explore more details and step-by-step visuals in the full documentation page here:
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.