For molecular modelers tackling complex protein-ligand interactions, balancing speed and precision in docking simulations can often feel like navigating a maze. The FITTED Suite SAMSON Extension, developed in collaboration with Molecular Forecaster, provides a streamlined solution, automating both covalent and non-covalent protein-ligand docking. This blog post explores how the FITTED Suite makes setting up non-covalent docking easy and efficient while emphasizing key functionalities, all within the SAMSON molecular design platform.
What is the FITTED Suite?
FITTED, which stands for Flexibility Induced Through Targeted Evolutionary Description, is a docking software that accounts for macromolecular flexibility, bridging water molecules, covalent functional groups, and even proton shifts during metal coordination. It combines a genetic algorithm with robust scoring functions to handle both metalloenzymes and other biomolecules like nucleic acids or GPCRs with ease.
The FITTED Suite in SAMSON wraps this software into an intuitive interface, assisting users in tasks like protein preparation, protein conformational ensemble setup, and ligand atom-typing. Whether you’re a researcher delving into drug discovery or a molecular modeler optimizing interactions, this suite is an invaluable tool.
An Example: Non-Covalent Docking with Thymidine Kinase
Let’s take a practical look at non-covalent docking involving the thymidine kinase protein complex (1E2K) and its ligand, (N)-methanocarba-thymidine.
1. Preparing and Importing the System
After launching SAMSON, simply open the provided tutorial file, 1E2K-A.sam. Pro tip: A quick drag-and-drop into the SAMSON workspace also works.
At this point, you’ll see the structural model in the Document view. This pane organizes molecular data into nodes, enabling intuitive interaction with the system’s elements.
Tip: If the Document view is hidden, reopen it via Interface > Document view or use the shortcut Ctrl+1 (Windows/Linux) or Cmd+1 (Mac).
2. Setting up the Docking System
Launch the FITTED Suite app from the Home > Apps > Biology menu. Start by defining the three essential components:
- Receptor: Select the
1E2Kmodel and set it as the receptor. Default parameters for water molecules and macromolecules (Protein) work well here. - Binding Site: Use the ligand
TMC 500to define the binding site. This can be easily found by searching forTMC 500in the Document view. - Ligand: Similarly, set
TMC 500as the ligand, ensuring the option to prepare the ligand (adding hydrogens, perceiving bond order) is enabled.
3. Running the Docking
Once the setup is complete, adjust a few parameters before docking:
- Set the number of runs to 2.
- If preferred, select the option to import only the best pose.
- Ensure the docking mode is set to Non-covalent.
You can also specify an output folder to save results. With everything in place, hit the Dock button to start the simulation. The progress log and current status will be displayed in-app.
4. Analyzing the Results
Once the process is complete, the results table will showcase the docking runs along with the best-ranked pose directly loaded into the Document view. Visualize the receptor with ribbons or add licorice visuals to analyze residues surrounding the ligand.
SAMSON also provides tools like the Protein-Ligand Interaction Analyzer and Hydrogen Bond Finder, allowing you to dive deeper into interaction dynamics. This additional analysis ensures that the fitted results align with the targeted scientific or therapeutic objectives.
Want to Learn More?
The FITTED Suite tutorial not only makes docking simulations simpler but enhances data visualization and interaction analysis for researchers. Explore the full documentation for a step-by-step guide, including instructions for covalent docking setups: https://documentation.samson-connect.net/tutorials/fitted/fitted-suite/.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Download SAMSON at https://www.samson-connect.net.