As molecular modelers, one of the persistent challenges is understanding the dynamic behavior of biomolecules — particularly how they open or close binding sites. These subtle structural changes are often key to understanding molecular functions, yet simulating them can be computationally demanding. Fortunately, the Normal Modes Advanced (NMA) extension in SAMSON offers an efficient and intuitive solution.
This powerful extension enables you to compute nonlinear normal modes of biomolecular systems, such as proteins, RNA, and DNA, with remarkable speed, thanks to the NOLB algorithm (J. Chem. Theory Comput., 2017, 13 (5), pp 2123-2134). By focusing on normal modes, you can isolate specific concerted motions in your structure, such as those that open a protein pocket, providing invaluable insight into binding site accessibility without computationally expensive molecular dynamics simulations.
How Does It Work?
To start, simply import a structure into SAMSON — for instance, the 1VPK PDB entry used in the tutorial — and launch the Normal Modes Advanced (NMA) module. You can then define parameters such as the number of desired modes, interaction cutoff distance, and the potential function to be applied. For now, an elastic network model is available, with plans for adding other options in the future.
One of the key advantages of this extension is the ability to focus on specific residues or the complete biomolecular system. Using SAMSON’s selection filter, you can easily select the regions of interest. Once selection is complete, the computation process begins, with a helpful progress bar and real-time updates displayed in the SAMSON status bar.
Within seconds, you can visualize normal mode results and observe how specific modes influence the conformation of the structure. A simple slider lets you explore the mode-specific motions interactively:
Combining and Fine-Tuning Modes
The NMA extension offers numerous ways to manipulate and combine modes for tailored exploration:
- Combine multiple modes by checking their corresponding boxes and playing them simultaneously.
- Individually adjust sliders during motion, enabling on-the-fly trajectory customization.
- Reset sliders independently or all at once using dedicated reset buttons.
Additionally, real-time minimization ensures physically realistic motions, with three minimization algorithms available for use. Here’s how these dynamics can look in action:
Fine-Tuning Amplitudes and Motion Types
By modifying the scaling factor, you can amplify or dampen the amplitude of your structure’s motion, offering further flexibility. The type of transformation can also vary between linear (translations only) or nonlinear (translations and rotations) to suit your analysis needs.
The motion speed and type (e.g., harmonic or non-harmonic) can also be adjusted, and stepwise buttons let you navigate the motion trajectory with precision:
Practical Applications
Whether you’re studying ligand binding, enzyme function, or conformational changes critical to molecular mechanisms, the Normal Modes Advanced extension shortens the path to valuable insights. Its simple interface and instant feedback make it accessible for both novices and experts in the field.
To explore further, detailed guidance is available in the original documentation.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.