One common bottleneck in molecular modeling is setting up a protein-ligand docking system—especially defining the binding site. Whether you’re preparing for non-covalent or covalent docking, determining the binding site accurately is crucial for reliable results and biological relevance. Luckily, the FITTED Suite Extension in SAMSON provides a few streamlined options for doing just that.
This blog post walks you through how to define a receptor’s binding site using the SAMSON interface, focusing on a use case from the Non-covalent docking: 1E2K tutorial. This practical example shows how to define a binding site effortlessly from an already bound ligand.
Why the Binding Site Matters
The binding site defines the region of the receptor where the ligand will be docked. Misdefining the site may result in irrelevant poses or failed docking attempts. Defining the site manually by coordinates or residue selection takes time and can be error-prone.
Efficient Binding Site Definition in SAMSON
The FITTED Suite in SAMSON allows you to define the binding site in three flexible ways:
- From Bound Ligand: Automatically define the site based on an existing ligand already bound to the structure.
- From Selection: Use atom selections to center the search grid.
- From Position: Use a movable sphere in the 3D Viewport to define the center manually.
Using a bound ligand is perhaps the most accurate and efficient choice when available. Here’s how it works in the context of the 1E2K structure (thymidine kinase bound to TMC 500).
Practical Workflow: Defining Binding Site from a Bound Ligand
- After opening the
1E2K-A.samfile, locate the bound ligand. In this case, it’sTMC 500. - Find it quickly via the search bar in the Document view, or expand the chain to locate the group.
- Double-click the
TMC 500group to select the entire ligand. - In the FITTED Suite, go to the Define binding site section, choose From bound ligand, and click Set.
Your binding site region will now be accurately defined using the coordinates and surroundings of the known ligand pose. This ensures that docking occurs in a biologically meaningful region of the receptor, reduces setup time, and minimizes potential for user error.
What If There’s No Bound Ligand?
Don’t worry. You can instead select a region of atoms near your site of interest or define the site manually with a sphere in the 3D Viewport. These give you flexibility when working with apo structures or when exploring potential allosteric sites.
Conclusion
Efficiently defining a receptor’s binding site isn’t just a convenience—it impacts the relevance and accuracy of your docking results. When a bound ligand is available, the FITTED Suite’s From bound ligand method is both simple and highly precise.
📘 Learn more in the official documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. Get SAMSON at https://www.samson-connect.net.