When working with molecular dynamics, modeling the transition pathway between two conformations—such as a ligand entering or exiting a binding pocket—is central to understanding molecular function. But here’s the catch: even when those conformations are relaxed local minima, the path in between often isn’t. It may just be a rough, linear interpolation or generated quickly from heuristics. This can lead to misleading interpretations of energy barriers and saddle points.
That’s where the Parallel Nudged Elastic Band (P-NEB) method comes in. This SAMSON extension lets you take an existing path or a set of conformations and optimize it into a smoother, more physically realistic transition pathway using energy minimization principles. Here’s why you might want to do that, and how.
What Problem Does P-NEB Solve?
Imagine you’ve run a docking simulation, or used a tool like Ligand Path Finder to get a rough set of conformations for ligand unbinding. These conformations probably give you a general idea of the path, but the atomic interactions along the trajectory might not be physically meaningful yet. Forces and energies between frames could be unrealistic, and simply interpolating between extremes may ignore key barriers or valleys in the energy landscape.
The P-NEB app refines linearly-connected structures by modeling them as images connected by virtual springs. It minimizes the energy of each configuration while maintaining equal spacing, identifying a minimum energy path (MEP) and sometimes the saddle point along the way.
Start with a Path (If You Can)
Technically, P-NEB can accept conformations or direct paths as input. But using a path is significantly faster. If you only have conformations, it’s a good idea to convert them:
Right-click on your selected conformations → Conformation > Create path from conformations
How to Apply P-NEB
Once your path is ready:
- Activate P-NEB via Home > Apps > All > P-NEB.
- Select your path node from the Document view.
- Choose your settings:
- Spring constant: 1.00
- Loops: 100
- Interaction model: Universal Force Field
- Optimizer: FIRE
- Parallel execution: ✅ Checked
- Click Run.
After initialization, you can monitor the status bar for convergence. The output will be a new, smooth path with optimized images. You can view and animate it by double-clicking it in the Document view.
Seeing the Difference
One of the most satisfying parts of this process is seeing the before and after. The refined transition path often reveals subtleties—an unexpected intermediate, a sharper energy barrier, a kink in geometry—that would otherwise stay hidden. It’s also suitable for communication: animated, optimized trajectories can add clarity to presentations or publications.
While the method doesn’t replace full-fledged dynamic simulations, it’s a practical way to quickly improve trajectory data, especially when computational resources or time are limited.
Want to dive deeper and access sample data to try this out? Check out the full P-NEB tutorial.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at www.samson-connect.net.