A Simple Way to Define Binding Sites for Docking in SAMSON

One of the most common challenges molecular modelers face when preparing docking simulations is the correct definition of the binding site. Whether you’re performing traditional ligand docking or exploring covalent inhibitors, inaccuracies in binding site selection can significantly affect your results. Fortunately, the FITTED Suite in SAMSON makes this process more intuitive and less error-prone.

This post guides you through defining the binding site efficiently using the SAMSON interface and the tools provided by the FITTED Suite extension. Specifically, we’ll look at the approach used in a non-covalent docking tutorial involving the 1E2K protein and its ligand TMC 500.

Why Binding Site Definition Matters

The accuracy of any docking protocol relies heavily on the definition of the binding pocket. Too large, and your results become noisy; too small or offset, and critical binding modes might go undetected. For crystal structures with co-crystallized ligands, there’s a convenient and reliable shortcut: use the known bound ligand to define the search space.

Using a Bound Ligand to Define the Binding Site

In SAMSON, the FITTED Suite allows you to create your binding site box directly from a ligand already bound in the protein structure. Here’s how it works:

  1. Load your structure (e.g., 1E2K-A.sam) into SAMSON. The TMC 500 ligand is already bound in this structure.
  2. Locate the ligand in the Document view. You can simply type TMC 500 in the search box and double-click on the group to select the ligand.
  3. Open the FITTED Suite from Home > Apps > Biology.
  4. In the “Define binding site” section, select From bound ligand and click the corresponding Set button.

A group referencing the TMC500 ligand

Other Options for Flexibility

If your system doesn’t include a bound ligand (e.g., for homology models or structures lacking a co-crystalized compound), the FITTED Suite provides two other methods:

  • From selection: Define a set of atoms and use their centroid as the center of the binding site sphere.
  • From position: Use a draggable sphere in the 3D Viewport to manually place the center of the search grid.

This level of flexibility is particularly useful when you’re exploring alternative binding modes or working with modeled structures where active sites are based on predictions.

Tips to Streamline Your Workflow

  • Use the Document view to quickly identify ligands or residues using search queries.
  • You can create groups for faster selection and organization, especially useful for recurring selections like binding site residues.
  • Make use of the zoom shortcut Shift + Space to focus on selected atoms or ligands.

By using a bound ligand to define your binding site, you ensure that your docking setup is aligned with experimental structures. This not only saves time during setup but also increases your chance of replicating known binding modes and scoring them accurately.

To explore this feature in more depth and view other helpful docking functionalities, visit the full tutorial at the official documentation: https://documentation.samson-connect.net/tutorials/fitted/fitted-suite/

SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON from https://www.samson-connect.net.

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