Specifying the binding site in protein-ligand docking simulations is often one of the most critical — and error-prone — steps in preparing a reliable docking study. Whether you’re working with co-crystalized structures or docking into an apo form, identifying the proper region where ligands should bind is essential.
In the FITTED Suite Extension for SAMSON, there are multiple intuitive ways to define a binding site. This flexibility helps users avoid guesswork and saves time by simplifying a step that is often done manually or externally. Here, we focus on a particularly useful workflow: defining the binding site “from bound ligand”, ideal for self-docking or when using structures with a co-crystallized ligand.
What Problem Does This Solve?
Molecular modelers often face tedious steps when setting docking grid centers manually, especially when working with new software or trying to interface various PDB files. Worse, incorrect grid definitions may waste compute resources or lead to misleading results.
With FITTED Suite in SAMSON, you can avoid this by directly selecting the co-crystallized ligand to auto-define the docking region. This eliminates manual parametrization of grid centers, ensuring reproducibility and reducing user error.
How to Define the Binding Site from Bound Ligand
Once you’ve opened your protein-ligand structure in SAMSON, simply follow these steps within the FITTED Suite:
- Locate the bound ligand in the Document view. In our example, that’s the
TMC 500ligand bound to the1E2Kthymidine kinase protein. - Use the search bar or expand the hierarchy to find and select the ligand.
- Double-click the ligand group to auto-select the entire molecule.
- Under the Define binding site section of the FITTED Suite, choose From bound ligand and click Set.
This auto-positions the docking search grid around the selected ligand’s centroid, helping streamline follow-up steps such as ligand preparation and docking execution.
Why This Matters
Besides accelerating preparation, this method ensures more reproducible experiments. It also encourages best practices in docking, such as performing self-docking to validate your system before moving to virtual screening. Combining it with the system setup workflow in FITTED Suite allows smooth transitions to receptor and ligand configuration.
Alternative options are available, such as repositioning the binding site manually using a 3D sphere or picking a centroid from selected atoms — but the bound ligand method is the most consistent when a co-crystallized structure is available.
To try this yourself, follow the full tutorial available in the documentation. It walks through the steps using the example PDB code 1E2K and the TMC 500 ligand.
Learn more in the full documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.