Finding accurate transition paths between molecular conformations is a key task in computational chemistry and molecular modeling. Yet, the process can be time-consuming and computationally expensive, especially if not properly initialized or accelerated. A major pain point for researchers is optimizing these paths efficiently and reproducibly, especially when studying complex processes like ligand unbinding.
The Parallel Nudged Elastic Band (P-NEB) app in SAMSON provides a streamlined way to improve transition paths, such as those generated from initial trajectory guesses. This blog post walks you through a very practical feature: applying P-NEB to existing ligand unbinding trajectories to enhance their quality—without starting from scratch.
Use Case: Improve Existing Ligand Unbinding Trajectories
Let’s say you’ve used the Ligand Path Finder to obtain a rough path of a ligand exiting a protein tunnel. This rough path might not represent the most physically plausible pathway. That’s where P-NEB comes in: it refines your trajectory into a minimum energy path by optimizing multiple intermediate structures in parallel.
Step-by-Step Guide
First, download a sample document with a precomputed path:
- Zinc ligand unbinding tutorial (smaller example)
- TDG–Lactose permease (1PV7–TDG) complex with unbinding path
Once loaded in SAMSON:
- Open the P-NEB app via Home > Apps > All > P-NEB.
- In the Document view, select the path node representing your ligand unbinding trajectory.
- In the P-NEB interface, set the following parameters:
- Spring constant: 1.00
- Number of loops: 100
- Interaction model: Universal Force Field
- Optimizer: FIRE
- Climbing image: optionally checked for saddle point refinement
- Parallel execution: checked
- Suffix: NEB
- Click Run.
What Happens Under the Hood
The app launches a parallel optimization for each image in the trajectory, maintaining even spacing between them with spring forces. This preserves structural continuity while finding a more physically meaningful unbinding path. The optimization is fast, especially with parallel execution enabled, and uses the climbing image strategy if you want to refine the high-energy transition state.
When to Use This
- Refining paths produced by interpolated conformations
- Improving outputs from path prediction tools
- Studying detailed energy landscapes and reaction mechanisms
Need More Control?
You can also apply P-NEB to a set of conformations instead of a path. However, this approach is slower and less recommended unless you’re customizing specific steps. If needed, you can convert conformations into a path directly in the interface via Conformation > Create path from conformations.
Conclusion
P-NEB in SAMSON helps you turn rough trajectories into realistic, energetically optimized transition paths—quickly and reproducibly. For ligand unbinding studies, this means more accurate mechanistic insights and robust data without excessive trial-and-error.
Learn more in the full documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.