If you’ve been trying to generate smooth transitions between protein conformations using interpolation tools and keep running into frustrating errors like: “Cannot proceed because the structure does not make one connected component,” you are not alone.
This issue is a common stumbling block for molecular modelers who work with experimental structures directly fetched from the Protein Data Bank. These structures often contain unnecessary components like water molecules, ligands, alternate residue locations, and ions. While this ancillary information can be valuable for some types of analysis, it can also prevent structure-processing tools from functioning properly—especially those that expect a single, connected macromolecule.
What’s the Problem?
The ARAP Interpolator in SAMSON is designed to generate realistic transition paths between molecular conformations. But the interpolation can only be computed if each conformation corresponds to a single connected structure. Even a stray water molecule can cause the algorithm to fail.
In short: your protein structure might look fine visually, but from a connectivity standpoint, it could be interpreted as multiple unconnected components.
The Quick Fix: Structure Preparation in SAMSON
To avoid these connectivity issues, SAMSON includes a streamlined preparation tool that cleans your protein structure and ensures proper format for interpolation.
Here’s how:
- After loading your structures (e.g.,
1DDTand1MDT) from the PDB via Home > Fetch, inspect and remove any extraneous chains. For example, retain only chainAof each file. - Use the Home > Prepare feature in SAMSON.
This preparation step will:
- Remove water molecules
- Eliminate ions and ligands
- Discard alternate conformations
By doing this, you leave only the clean, connected amino acid chain that ARAP Interpolation—and many simulation tools—require for reliable results.
A Closer Look at the Error
If you skip the preparation step, you might encounter major slowdowns in your workflow. The warning "structure does not make one connected component" is difficult to interpret at first because there’s often no visual cue. That’s why proactively cleaning the structure is the better route.
The structure below shows a case where chain B from 1MDT needs to be removed before proceeding:
Helpful Tips
- If you’re unsure what’s causing the error, double-check that only one chain is present in your protein.
- Be especially vigilant with prepared structures downloaded from other sources—they might contain lipids, solvents, or cofactors that aren’t immediately obvious.
- Use the Document view in SAMSON to inspect and manage the structure hierarchy.
Conclusion
By understanding and addressing this preparation step, you can significantly improve your experience working with molecular interpolation tools. It’s a small task that removes a major obstacle and improves compatibility with downstream applications like simulations and conformational analysis.
You can explore more details in the full tutorial here: ARAP Interpolation for Protein Structures – SAMSON Documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at samson-connect.net.