One of the persistent challenges in computational structural biology is predicting how to open or close a binding pocket in a macromolecule like a protein. Whether you’re studying allosteric effects, conformational gating, or simply trying to dock a ligand into a less-accessible cavity, manually modeling such conformational changes can be time-consuming and unreliable.
Fortunately, the Normal Modes Advanced module in SAMSON offers a practical solution. It allows you to automatically identify combinations of normal modes that open or close a user-defined region—all through an intuitive interface.
What does this mean in practice?
Imagine you’re working with a protein where the ligand-binding site appears closed in the crystal structure. Instead of arbitrarily applying torsion angles or biases, you can now define the binding pocket by selecting a group of residues or atoms—then let the extension do the hard work of identifying the motions that best open it.
Step-by-step uses of the Structure Definition tab
Within the Structure Definition tab of the Normal Modes Advanced module:
- Select the atoms or residues that define the region you want to open. This could be a ligand-binding site or allosteric pocket.
- Use the interface to compute the best combination of normal modes that causes measurable structural displacement in that region.
- Watch the visual feedback: the module will animate how the protein naturally opens at the desired location, powered by a combination of precomputed nonlinear normal modes.
This isn’t about visual gimmicks—these motions are grounded in the NOLB algorithm, making use of physics-based approximations to suggest energetically reasonable deformations.
You can go further…
Once you’ve found a motion that opens your pocket, you’re not limited to viewing the result. You can also:
- Define a target structure and ask the extension to compute the combination of modes that approximates this target as closely as possible. This is useful when you’re trying to mimic an experimentally known open form, or hypothesized conformation.
This approach replaces trial-and-error refining with a more systematic and informed method for exploring conformational transitions. Because the Normal Modes Advanced Extension uses nonlinear normal mode analysis, it captures both translational and rotational deformations—often missed by basic elastic network models.
Why this matters
Manually tweaking molecular structures to achieve an open binding state is not only inefficient—it can also lead to unrealistic conformations. With the method described here, you benefit from an informed search over the structure’s intrinsic flexibility.
This makes it particularly helpful for users in drug discovery, protein engineering, or anyone curious about conformational change without the overhead of molecular dynamics simulations.
Learn more and explore the full tutorial on computing nonlinear normal modes 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.