For molecular modelers involved in drug discovery or structural biology, accurate non-covalent docking of ligands to protein binding sites can often be a challenging but critical task. The need for efficient, automated tools to simplify this workflow is acute. Thankfully, the FITTED Suite SAMSON Extension is designed to simplify non-covalent docking tasks, offering precision and flexibility while handling protein and ligand preparation automatically.
Below, we’ll explore the essential steps for setting up and conducting non-covalent docking using SAMSON and the FITTED Suite. By following this guide, you can streamline your docking workflows and focus more on analyzing results and driving your projects forward.
Step 1: Preparing the Project
To begin, start SAMSON and open the tutorial file 1E2K-A.sam, which provides a structural model of a thymidine kinase protein (1E2K, chain A) bound to the ligand (N)-methanocarba-thymidine (TMC 500). This file is accessible within the FITTED tutorial archive.
The document will display the protein structure in SAMSON’s intuitive 3D viewport while the hierarchical data of molecules, atoms, and related nodes will be seen in the Document view. If the Document view panel is closed, activate it via Interface > Document view or by using the shortcut Ctrl + 1 (Windows/Linux) or Cmd + 1 (Mac).
The FITTED Suite automatically fixes common structural issues, so preparing the system often requires minimal manual intervention. However, it’s always a good idea to check for alternate atom locations or missing structural elements as necessary using SAMSON’s Prepare tool.
Step 2: Defining the Docking System
Open the FITTED Suite app from SAMSON’s menu under Home > Apps > Biology. You can also use the Find everything… search box. The docking process begins by defining three key elements: the receptor, the binding site, and the ligand.
Set the Receptor
First, select the structural model of the protein (1E2K-A) in the Document view. Then, under the Set receptor panel in the FITTED Suite interface, choose From document and click Set. Retain the default Water molecules and Macromolecules parameters.
Define the Binding Site
To identify the docking binding site, choose From bound ligand (this option uses the centroid of the bound ligand as the center of the search grid). Locate the ligand TMC 500 in the Document view and select it. Then click the Set button.
Select the Ligand
Under the Set ligand section, choose From document. Select the TMC 500 ligand again within the document. Check the box to prepare the ligand, which automatically perceives bond orders, adds hydrogens, and optimizes the structure. Click Set to confirm.
Step 3: Configuring and Running the Docking
Now it’s time to specify docking parameters. For this example:
- Set the number of runs to 2 for a quick analysis.
- Optionally, check Import best pose only to limit output to the best docking result.
- Choose Non-covalent mode as the docking type.
Define the output folder where results and logs will be saved, then click Dock to start the calculation. Docking may take a couple of minutes, with progress displayed in the interface.
Step 4: Reviewing the Results
Once complete, results will appear in the Results table and the document will auto-load the processed receptor (1E2K_pro) and docked ligand poses. Hide the initial structures by unchecking them in the Document view for clarity.
Visualize the system using Ribbons or other display models from the Visualization menu. Add labels or licorice visuals to residues near the binding site for a deeper understanding of ligand interactions. SAMSON’s integrated tools allow for measurement and insight into contact areas, binding residues, and hydrogen bonds.
Conclusion
The FITTED Suite’s automation makes it an accessible and powerful tool for researchers looking to perform precise non-covalent docking studies efficiently. To learn more, visit the full documentation page at https://documentation.samson-connect.net/tutorials/fitted/fitted-suite/.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at https://www.samson-connect.net.