In this tutorial, we will show you how to use the ARAP Interpolation Path Extension to generate a path between two protein structures or conformations within a few seconds thanks to ARAP (As-Rigid-As-Possible) interpolation.
References: Minh Khoa Nguyen, Léonard Jaillet, and Stéphane Redon. As-Rigid-As-Possible molecular interpolation paths. Journal of Computer-Aided Molecular Design (2017) 31: 403. https://doi.org/10.1007/s10822-017-0012-y
Requirements
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- ARAP Interpolation Path Extension
Before starting the tutorial, we would like to ask you to download this file (ArapInterpolation) which contains the necessary files for this tutorial. After extracting it, you will have two PDB files: 1ddt_A.pdb and 1mdt_A.pdb.
Tutorial
Our goal is to use the ARAP Path app to generate a path from 1ddt_A.pdb to 1mdt_A.pdb. These are two conformations from chain As of the PDB entries 1DDT and 1MDT in the Protein Data Bank, respectively, for Diphtheria Toxin.
Loading protein structures
Run SAMSON. Load 1ddt_A.pdb and 1mdt_A.pdb files from the provided archive. In the Document View, select the 1ddt_A structural model and if the structure contains non-protein nodes then in the main menu click Select menu > Biology > Receptors to select only the receptor/protein (see the note below). Then in the main menu click Edit menu > Add > Conformation, and name the new conformation 1ddt_A. Do the same for the 1MDT_A structural model and name the conformation as 1mdt_A.
Note: if your system has non-protein structures then you will need to either delete them or select only protein structures for the conformation creation via Select menu > Biology > Receptors. To delete non-protein structures you can use the Select menu to select them (e.g., water, ligands, ions) and then delete selections. See User Guide: Selecting for more information.
The files in the archive were already prepared for you to contain only protein structures.
Executing ARAP Path app
Open the ARAP Path app via Home menu > Apps > Biology > ARAP Path Interpolation.
In the app, click Get conformations from the active document. Then, in the Start and Goal lists, select 1ddt_A and 1mdt_A, respectively.
Under Construct ARAP vertices by matching, check 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. The descriptions of all the options are as follows:
- 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.
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. The descriptions of all the options are as follows (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.
Check the box of 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 (note that the start and goal conformations are also included in the path).
Now click Apply to run the ARAP interpolation
In the end, you should have the settings as shown in the below figure.
Results
Viewing the edge construction type
After the interpolation, the information of the run will be summarized in the box at the bottom of the app (the text area marked with Other information… in the last figure). A new visual model (named ARAP edges in the Document View) is also created to show the ARAP edges. In this visual model, the colors of the edges are the same as the squares that are beside the checkboxes of ARAP edge construction types in the app window.
You can always show/hide the ARAP edges in the viewport by checking/unchecking the ARAP edges visual model in the Document View.
To better see the ARAP edges, you can hide the stick-and-ball representation of 1DDT_A and 1MDT_A in the Document View by unchecking their boxes.
Adding the secondary structure visualization
If you haven’t chosen to create a secondary structure visual model on loading of PDB files, then you can easily add them by selecting a structural model and clicking Visualization menu > Visual model > Ribbons. See User Guide: Visualizing for more information.
Viewing the path conformations
In the ARAP Path app, manipulate the slider or the number in the box next to it for viewing the conformations along the path (see the animation below).
Exporting the path
For exporting as a SAMSON path, click the Export path button, and a path node with the name “Path” will be created in the Document View.
For exporting as PDB files, click Export pdb, then select a folder you want to export them to. Each conformation will be saved as a PDB file with a sequence ID at the end of the file name.
What’s next?
You can, for example, perform Umbrella Sampling based on the generated path using GROMACS Wizard (see GROMACS Wizard tutorial).
If you have any questions or feedback, please use the SAMSON forum.