One common challenge in molecular modeling is identifying the motions that allow biomolecules, such as proteins, to adopt conformations that open or close binding pockets. This task is particularly relevant when working on ligand docking, drug design, or analyzing functional motions. Instead of guessing how a structure could change, wouldn’t it be useful to systematically search modes that *drive* the transition toward the desired form?
The Normal Modes Advanced Extension in SAMSON offers a feature that supports exactly this: computing combinations of normal modes that open or close selected structural regions. This tutorial-based article provides an introduction to the Structure Definition feature that helps you steer molecular conformations toward specific goals.
Targeting a Pocket or Structure
Suppose you have a protein structure where access to the active site is blocked. You want to model an open conformation—for example, to prepare the system for ligand binding. In SAMSON, you can define a target using either atoms or residues that make up the desired open pocket. This forms the basis for your structural goal.
Once you’ve defined the target, the Normal Modes Advanced Extension searches for the best combination of nonlinear normal modes (NNMs) that deform the molecule in this desired direction. All of this is done using the NOLB algorithm, which is efficient and able to capture both translations and rotations involved in realistic biomolecular motions.
From Modes to Conformations
After computing the best combination of modes, you can visualize the motion toward the target. The transformation may be applied gradually, with interactive sliders allowing you to explore partial or full deformations, as well as try different combinations of modes. This helps you better understand how specific dynamic processes happen, and what parts of the structure are involved.
Why It Matters
Being able to guide a molecular system toward an open or closed state based on a defined region significantly speeds up hypothesis testing. Instead of running long molecular dynamics simulations in hopes of observing these motions, you can now generate plausible open or closed conformations in seconds. These conformations can then be used for follow-up tasks like docking or comparative studies.
Additionally, because the tool supports nonlinear modes, it captures complex conformational changes—not just small, linear vibrations around an equilibrium. This makes it ideal for studying biologically significant motions, such as loop openings, domain rearrangements, or induced-fit behavior.
To Learn More
The Structure Definition capability provides a focused and efficient way to study function-related structural transitions. It’s especially useful when working with partially occluded active sites, flexible loops, or proteins that exist in multiple conformational states.
To explore this feature in detail, visit the full tutorial at the official documentation: 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.