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Generate a Transition Path Between Protein Structures with ARAP Interpolation#

Use the ARAP Interpolator extension in SAMSON to generate within a few seconds a smooth, realistic path between two protein conformations using As-Rigid-As-Possible (ARAP)1 interpolation. It can be used as part of the workflow for applications in conformational analysis, transition state modeling, or umbrella sampling setup.

ARAP Interface This image is from the use case tutorial on computing the opening motion of the SARS-CoV-2 spike where ARAP Interpolation was used to generate an interpolated path between open and closed states of the spike protein.

Why Use It?#

  • Compute continuous structural transitions in seconds.
  • Visualize and export intermediate conformations.
  • Build realistic reaction coordinates for free energy simulations.
  • Aligns and places conformers using a biologically meaningful geometric model.

Getting Started#

  1. Log into SAMSON Connect.
  2. Visit the ARAP Interpolator Extension page and click Add.
  3. Restart SAMSON - your extension will be ready to use.

Step 1 - Loading protein structures#

Fetch the example structures in SAMSON:

  • Open Home > Fetch.
  • Input 1DDT 1MDT in PDB or PDB (mmCIF).
  • Click the corresponding Load button.

1DDT and 1MDT represent two conformations of the Diphtheria Toxin (chains A and B). You'll work only with chain A:

  • Expand 1MDT in the Document view to see the chain B.
  • Select and delete chain B (click Del or click erase erase in the popup context toolbar).

Delete chain B from 1MDT

Our goal is to generate a path from the chain A of 1DDT to chain A of 1MDT.

Then run Home > Prepare to clean both structures (remove alternate locations, water, ligands, ions).

Need Help Preparing Structures?

Refer to the Protein Preparation & Validation tutorial for guidance.

Step 2 - Create Conformations#

To use ARAP Interpolator, create conformations from the two cleaned structures:

  • Select the structure, e.g. 1DDT, in the Document view.
  • Click Edit > Conformation and name it e.g. 1DDT A.

Do the same for 1MDT and name its conformation as 1MDT A.

These conformations serve as the start and goal of the interpolation path.

Tutorial document

Step 3 - Run the ARAP Interpolation App#

Open the app via Home > Apps > Biology > ARAP Path Interpolation.

Choose Conformations:

  • Click Get conformations from the active document.
  • Choose Start: 1DDT A and Goal: 1MDT A.

Matching Atoms:

For Construct ARAP vertices by matching, choose All except hydrogens. This option considers only non-hydrogen atoms for matching the atoms between the start and goal conformations. The matched atoms in the start conformation will be considered as ARAP vertices.

Matching Atoms Options

  • All atoms: consider all the atoms for matching.
  • All except hydrogens: consider all the atoms except hydrogens for matching.
  • Only α-carbons: consider only α-carbon atoms for matching.
  • Only backbone atoms: consider only backbone atoms for matching.

Building ARAP Edges:

Check:

  • from bonds in the Start structure - creates ARAP edges considering all the bonds in the start structure.
  • Try connecting α-carbons before and after missing residue segments - creates an ARAP edge between the α-carbon atoms before and after each segment of missing residues in the start structure.

These options define how connectivity and continuity are built across conformations.

Under Construct ARAP edges, check the boxes of from bonds in the Start structure and Try connecting α-carbons before and after missing residue segments. The former creates ARAP edges considering all the bonds in the start structure. The latter creates an ARAP edge between the α-carbon atoms before and after each segment of missing residues in the start structure.

Building ARAP Edges Options

If multiple options are checked, the algorithm will add the ARAP edges in the order from top to bottom.

  • from bonds in the Start structure: create ARAP edges based on the covalent bonds in the start structure.
  • from consecutive α-carbons: create ARAP edges between α-carbons in consecutive residues of the start structure.
  • from hydrogen bonds with cutoff distance: create ARAP edges for hydrogen bonds whose lengths are shorter than the cutoff distance in the start structure.
  • atom pairs whose distances are within a range: create ARAP edges for atom pairs whose distances are within the specified range in the start structure.
  • from α-carbon pairs whose distances are within a range: create ARAP edges for α-carbon atom pairs whose distances are within the specified range in the start structure.
  • Try connecting α-carbons before and after missing residue segments: create ARAP edges for the α-carbon atoms before and after each segment of missing residues in the start structure.

Preprocessing:

Check Perform alignment before interpolation. This will align the start conformation with the goal conformation before performing ARAP interpolation.

Set "Number of path conformations" to 20 to generate a path of 20 conformations (start and goal are included).

You should have the settings as shown in the below figure.

ARAP interface with results

Click Run to compute the path interpolation.

Step 4 - Analyze and Export Results#

After the interpolation is done, the computation information is summarized in the Other information... box at the bottom of the app.

Visualize Pathlines#

Use the slider in the app to scrub through the interpolated conformations:

ARAP results

Visualize Edge Construction#

A visual model ARAP edges is created. Colors correspond to the chosen construction types.

  • Toggle visibility in the Document view.
  • View edge colors to understand path construction logic.

You can always show/hide the ARAP edges in the viewport by checking/unchecking the ARAP edges visual model in the Document view.

Visualizations in SAMSON

Learn more about visualizations in SAMSON from User Guide: Visualizing.

Export options#

  • Export path: saves a path (trajectory) object in the current SAMSON document.
  • Export PDB: outputs the whole path into a PDB file and each conformation as a sequential PDB file.

Troubleshooting#

If you get the following error when trying to run the computation with ARAP interpolator: "Cannot proceed because the structure does not make one connected component". It means that you have one or more nonconnected structures in one of the systems, e.g., because water, ions, ligands were not removed. Run Home > Prepare to clean both structures (remove alternate locations, water, ligands, ions).

Next Steps#

Use this ARAP-generated path as input for simulation techniques:

Need Help?#

Have questions or feedback? Feel free to reach out via the Forum, via e-mail, via the Feedback button in SAMSON, or by directly discussing with us.

References#

  1. Minh Khoa Nguyen, Léonard Jaillet, and Stéphane Redon. As-Rigid-As-Possible molecular interpolation paths. Journal of Computer-Aided Molecular Design (2017) 31: 403. ↩