Molecular modelers often face the challenge of understanding how proteins or macromolecular complexes open up to allow small molecules to bind. Deciphering this process is key in fields like drug discovery and biomolecular engineering—but simulating these motions can be time-consuming and computationally expensive.
The Normal Modes Advanced extension in SAMSON offers a fast and user-driven way to explore conformational changes that open or close binding sites, using nonlinear normal mode analysis. This functionality is particularly useful when you have a clear idea of what a target pocket or conformation looks like—and you want to understand which internal motions get you there.
From Motions to Mechanism
The “Structure Definition” feature allows you to explicitly define a pocket—either by selecting specific atoms or residues—and then compute the best combination of normal modes that move the structure to either open or close that pocket. This removes much of the guesswork usually involved in inspecting normal modes one at a time.
The process is interactive and visual: as you define your target conformation or pocket, SAMSON calculates an optimal combination of nonlinear modes that approach this goal. This saves time and provides valuable insight into functional motions that may otherwise be missed using RMSD-based methods or brute-force molecular dynamics.
Targeting a Conformation
The same module goes a step further. In the Structure Definition tab, you can supply a complete target conformation instead of just a binding pocket. SAMSON then searches for the best-suited combination of normal modes that deforms your system toward this target. This reverse-screening style of motion prediction can be especially powerful when working with cryo-EM or NMR data offering different conformational snapshots.
Why It Matters
Instead of inspecting dozens of modes manually and trying to guess which will deform your system in the intended way, this tool elevates the workflow to an inverse problem: “Here’s what I want—what combination of modes gets me there?” This is not only faster but supports a hypothesis-driven approach to molecular flexibility.
Whether you are studying ligand gating, domain motion, or structural transitions, the structure definition functionality in Normal Modes Advanced may turn what previously required long simulations into a few minutes of guided exploration.
To learn more about how this works, check 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.