One common challenge in molecular modeling is illustrating conformational transitions—especially when you only have two experimental structures available. Whether for presentations, publications, or hypothesis generation, animating molecular transitions can help reveal critical insights quickly. But interpolating between two states manually and making the trajectory look plausible is often tedious or requires writing custom scripts. What if you could compute smooth conformational transitions directly from a molecular editor, without switching tools?
This is exactly the problem addressed in a practical example by the SAMSON molecular design platform, which shows how to compute an opening motion for the SARS-CoV-2 spike protein starting from just its closed and open experimental conformations (PDB: 6VXX and 6VYB).
Why compute a trajectory between states?
Often, protein structures are only available in limited states, usually a few stable conformations captured by crystallography or cryo-EM. However, molecular function often lies in the motions between those states. For example, the SARS-CoV-2 spike opens up to expose its receptor-binding site—understanding how this happens reveals potential intervention points for drug and antibody design.
How it works in SAMSON
Using SAMSON, you can start from the open and closed spike conformations and interpolate the motion using:
- ARAP Interpolation Path module – which generates an as-rigid-as-possible transition.
- P-NEB module – which optimizes that transition using an energy-based approach (Parallel Nudged Elastic Band).
A full animation is created, and the platform visualizes how the spike opens and closes in various orientations, such as side and top views.
SAMSON even provides downloadable trajectory files in PDB or SAMSON formats for further analysis or visualization in other platforms.
What’s actually being calculated?
The SAMSON documentation gives details on the pipeline researchers followed. In brief:
- They preprocessed the two spike structures (added hydrogens, fixed sugar bond orders).
- They used the ARAP module to generate a geometric interpolation from the open to the closed state.
- Since the structures had some residue mismatches, they refined the paths to ensure compatibility.
- Finally, they optimized the motion using the P-NEB module, resulting in a plausible, smooth conformational change.
Why molecular modelers should care
This pipeline saves hours of manual interpolation or simulation setup. Importantly, it provides an immediately useful structural trajectory that can aid in tasks like antigen exposure analysis, neutralizing antibody docking, or educational visualization. Having a ready-to-download, visually inspectable set of conformations from two crystal structures is helpful beyond COVID-19-specific cases.
Learn more in the full documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON here.