One of the most common sources of error in protein docking simulations is starting with an improperly prepared protein structure. Even a few misplaced atoms, missing hydrogens, or leftover water molecules can impact docking results and mislead analysis. If you’re using SAMSON for integrative molecular modeling and planning to run docking with the Hex plugin, here’s how to properly prepare your protein system before docking starts.
Why protein preparation matters 🧬
Docking simulations are sensitive to the quality of the input models, especially when it comes to protein structures. Structures obtained from crystallographic data, like those in PDB files, often need cleaning and completion before they are docking-ready. Failing to prepare proteins can result in unrealistic docking poses, incorrect binding interfaces, and ultimately, wrong conclusions.
Key steps in SAMSON to prepare your protein
SAMSON makes it easy to carry out all key preparation steps in one place. Go to Home > Prepare and make sure you check the following:
- Remove atoms with alternate locations: Ensures that only one atom position is kept for ambiguous side chains or backbones.
- Remove water, monatomic ions, and ligands: These may interfere with docking and should be removed unless directly relevant.
- Add hydrogens: Necessary for calculating electrostatic interactions. Only skip this if custom protonation is already applied.
Fixing problems with the structure
Sometimes protein structures contain missing residues, incomplete side chains, or other anomalies. You can repair these with the help of the PDBFixer Extension. This tool not only restores good geometry by rebuilding residues and atoms, but also allows you to customize hydrogen addition based on pH levels. This is particularly useful if you want to mimic biological conditions more closely.
For more complex fixes like adding loop regions or validating the geometry of your system, SAMSON also provides tutorials such as the Protein Preparation & Validation tutorial, which walks you through detailed workflows.
Helpful visual tips for better control
If you’re unsure whether your model is properly prepared, visualization can help. Use the Document view to inspect whether atomistic representations or ribbon models are shown. If ribbons are missing, you can add them by selecting your protein and navigating to:
Visualization > Visual model > Ribbons
Hydrogens are small and hard to see, so make sure you have proper settings in your visual model to inspect them. You can toggle the visibility of elements in Document view.
Note
The system used in the Hex docking tutorial already has water removed and hydrogens added, so it’s docking-ready out of the box. But most real-world cases won’t be as clean.
Conclusion
Making sure your proteins are clean and chemically complete is a small time investment that can save you from misleading docking results and wasted computing time. Whether you’re working from a downloaded PDB file or your own structure, use SAMSON’s “Prepare” dialog and PDBFixer to set your system up for success.
To dive deeper into full docking workflows, check out the original documentation: Protein Docking with Hex Extension.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.