One of the recurring challenges for molecular modelers is illustrating and analyzing the conformational changes of large biomolecular structures. When representing motion between two conformations—like open and closed forms of a protein—preparing a realistic and useful trajectory can be time-consuming. Especially when the structures differ in the number of residues or contain glycosylations and other modifications. If you’ve tried doing this before, you know how tricky it can get.
To help with this, the team behind SAMSON has made available a full trajectory showing the transition of the SARS-CoV-2 spike protein from its closed (inactive) state to its open (ACE2-binding) state. This trajectory can be downloaded and used directly in structural or mechanistic studies—and it could be particularly useful for anyone preparing animations or setting up simulations that require intermediate states.
The value of the trajectory
The spike mediates viral entry into host cells and undergoes large conformational changes to expose or conceal the receptor-binding domain. The motion of the spike is not merely a curiosity; it influences infectivity and immune recognition.
However, available static PDB structures—such as 6VXX (closed) and 6VYB (open)—only capture the endpoints. Reconstructing a plausible motion trajectory between them requires extra steps that many researchers may not have time to carry out manually. What’s more, glycosylation and differences in residue count between conformations make these steps non-trivial.
What’s inside the trajectory
The SAMSON team reconstructed the spike transition pathway using specialized modules designed for interpolating biomolecular motion: the ARAP (As-Rigid-As-Possible) Interpolation Path and the P-NEB (Parallel Nudged Elastic Band) method. The final output is a smooth trajectory, compatible with SAMSON and available in multiple formats:
Opening the SAMSON file gives access to:
- The starting (open) and ending (closed) conformations
- The smooth interpolated transition pathway between them
- Visual animations that demonstrate this transition in multiple orientations
It looks like this in SAMSON’s Document view:
Double-clicking the trajectory nodes lets you animate the opening and closing motion interactively.
How it was built
The team first corrected sugars’ bond orders with a Python script, added hydrogens, and minimized both conformations in SAMSON. The ARAP module generated an initial interpolation, followed by refinement with the P-NEB module. The final trajectory took less than 20 minutes to compute on a laptop and provides a clear visual of how the spike changes its conformation—a process essential for binding the ACE2 receptor.
Try it yourself
If you are working with viral fusion proteins or need real motion data to plan docking strategies, simulate transitions, or prepare presentations, this trajectory is available as is. While not experimentally validated, it can serve as a visual guide or a starting point for further modeling and refinements.
Want to explore the whole setup or compute your own trajectories? Read the full documentation here: https://documentation.samson-connect.net/tutorials/sars-cov-2/coronavirus-computing-the-opening-motion-of-the-sars-cov-2-spike/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download the platform at https://www.samson-connect.net.