One common challenge when studying macromolecules is understanding and predicting how biomolecular structures open and close their active or binding sites. Whether you’re designing a drug or investigating conformational transitions, this dynamic behavior is crucial — but simulating it can be computationally expensive and technically complex.
The Normal Modes Advanced Extension in SAMSON offers a practical solution to this problem with an intuitive feature: the Structure Definition tab, which lets you find combinations of normal modes that open or close a defined region, such as a binding pocket.
Why this matters ðŸ§
Imagine starting with a closed protein conformation and wanting to explore how it might open to accommodate a ligand. Traditional molecular dynamics simulations can take a long time and might not even sample the right conformational space. But with normal mode analysis, and more specifically nonlinear modes (which include both translations and rotations), you can explore such conformational changes much more efficiently.
How it works
In SAMSON’s Normal Modes Advanced Extension, the Structure Definition feature is designed specifically to help users:
- Define a region of interest (e.g., residues or atoms forming a pocket).
- Set a target conformation or desired opening/closing movement.
- Find the optimal combination of normal modes to achieve this movement.
This feature is illustrated below, where a user defines a pocket and discovers a set of modes that cause that pocket to open:
But it goes further. Once you define a target structure, the tool will automatically seek the best combination of modes to reach that structure from the starting conformation:
Practical uses
Some examples where this can be particularly useful:
- Drug docking preparation: Finding conformations in which binding sites are accessible.
- Loop flexibility analysis: Studying how loops move in response to ligand binding.
- Conformational transitions: Predicting motion pathways from one structure to another.
What makes it valuable
This approach gives a guided, interpretable way to explore functional motions in molecules. You don’t have to blindly tweak sliders or simulate for hours. Instead, you define what you want (an open pocket, for example), and let the algorithm do the work of combining non-linear modes to reach that configuration.
For computational biologists, molecular designers, and structural bioinformaticians, this capability can save time and provide insights about structure-function relationships that are otherwise hidden.
To learn more about how to define structures and manipulate them using normal modes, visit the full documentation 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 download SAMSON at https://www.samson-connect.net.