For molecular modelers, setting up and running protein-ligand docking workflows can be a daunting task. Between preparing proteins, defining binding sites, and configuring ligands, the steps can quickly become cumbersome and error-prone. That’s where the FITTED Suite SAMSON Extension comes in, making the entire process much more manageable within the powerful SAMSON Integrative Molecular Design Platform. In this blog post, we’ll walk through the streamlined process of using FITTED Suite for performing non-covalent docking, a common workflow in structure-based drug discovery.
Understanding FITTED Suite
The FITTED Suite was developed in partnership with Molecular Forecaster, integrating their state-of-the-art FITTED Docking Software. This tool automates essential protein-ligand docking tasks, from protein preparation to ligand orientation optimization. Its genetic algorithm considers the flexibility of macromolecules, proton shifts, and even bridging water molecules, providing excellent scoring functions and docking precision. Let’s investigate how to perform non-covalent docking using the FITTED Suite in SAMSON.
Step-by-Step Guide for Non-Covalent Docking
1. System Setup
Begin by adding the FITTED Suite Extension from the SAMSON Connect interface and downloading the FITTED tutorial archive. Launch SAMSON, then open the provided 1E2K-A.sam file. This file contains a structural model of a thymidine kinase protein (1E2K) with a bound ligand (TMC 500).
Once the document is open, you’ll see the structural hierarchy in the Document view, where molecules, folders, and visual models are organized. If your Document view is not visible, open it via Interface > Document view or on Windows/Linux use Ctrl+1 (or Cmd+1 on Mac).
2. Defining Receptor, Binding Site, and Ligand
- Receptor: Select the 1E2K structural model in the Document view, then in the Set receptor section of FITTED Suite, select From document and click Set.
- Binding Site: Because this is a self-docking workflow, use the bound ligand to define the binding site. Select the
TMC 500ligand (part of chain A) from the Document view, then in Define binding site choose From bound ligand and click Set. - Ligand: Similarly, select
TMC 500as the ligand. In the Set ligand section, choose From document and click Set. Ensure the preparation option (adding hydrogens and perceiving bond orders) is checked.
3. Running the Docking
Specify the docking parameters:
- Number of runs: 2
- Optionally, check “Import best pose only”
- Set docking mode to Non-covalent
At the top of the app, provide an Output folder to save results. Once you’re ready, click Dock. The docking process should complete in a few minutes, with the current stage displayed on the button and logs visible below.
4. Reviewing Results
After completion, results appear in the results table and the document view. You’ll see the processed receptor (1E2K_pro) with added hydrogens and the docked ligand pose. For better visualization, hide the initial structure by unchecking it in the Document view. To understand docking better, you can analyze ligand-receptor interactions further.
Conclusion
By following this streamlined workflow, researchers can bypass common pain points in protein-ligand docking and focus on understanding interaction results. The detailed automation capabilities and flexibility of the FITTED Suite within SAMSON make it a practical solution for molecular modelers. To learn more about protein-ligand docking with FITTED Suite, visit the official documentation page.
Note: SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.