Computing conformational changes in large macromolecular systems is often time-consuming and computationally intensive. What if you need a representative trajectory between two known structures but can’t afford to run costly molecular dynamics simulations?
For molecular modelers looking to visualize and analyze conformational motions—without relying on high-performance computing or long simulations—the ARAP and P-NEB modules in SAMSON offer a practical and fast alternative. In this post, we dissect how such a motion was computed between the closed and open states of the SARS-CoV-2 spike protein using just two known PDB structures, leading to shareable, analyzable trajectories in minutes.
Simplifying Motion: From States to Trajectories
The challenge? Generating a plausible transition pathway between two experimental structures (PDB IDs 6VXX and 6VYB), corresponding to the closed and open conformations of the SARS-CoV-2 spike protein. These two models differ in their sets of residues and present different challenges in terms of structure preparation and interpolation.
To bridge between these states, the workflow used:
- Structure preparation – correcting sugar bond orders with a Python script and adding hydrogens.
- Energy minimization – to relax structures before interpolation.
- Path interpolation – using the As-Rigid-As-Possible (ARAP) Interpolation Path module which, as its name implies, generates a path assuming rigid motion within molecular fragments.
- Trajectory refinement – using the Parallel Nudged Elastic Band (P-NEB) module to optimize the path, making the transitions smoother and more physically plausible.
This strategy offers a lightweight but effective alternative to full-blown simulations. The results can be animated, exported, and analyzed using standard molecular formats (PDB, SAMSON .sam files), and the whole process took less than 20 minutes on a normal laptop.
What You Get: Trajectories and Insight
The authors of the documentation provided downloadable versions of the spike’s transition trajectory:
These can be used to study spike behavior, analyze structural rearrangements, or generate visuals for communication and teaching.
Why This Matters
This workflow solves a recurring pain point in computational structural biology: generating animations and intermediate conformations without heavy simulation demands.
It’s especially useful when:
- You want to illustrate conformational changes in publications or presentations.
- You need to explore possible transition states.
- You’re building hypotheses about ligand accessibility or epitope exposure.
Of course, as noted in the documentation, the trajectory is not experimentally verified and should be treated as an illustration. That said, it can be a powerful starting point for exploratory modeling or even machine learning applications.
To explore the full tutorial and download the files, see the original documentation page.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.