One of the most common pain points for molecular modelers starting with protein docking is the setup of the system. Performing docking without carefully preparing your molecular models can lead to wasted computing time and misleading results. If you’ve ever experienced strange results or unexpectedly long calculation times when docking proteins, it’s likely due to an improperly prepared input.
In this post, we’ll walk through how to correctly prepare your protein systems in SAMSON before launching docking with the Hex Extension. This step is fast, reproducible, and eliminates common errors before they become problems later on.
Why proper preparation matters
Protein structures from public databases are often incomplete or contain elements that are not relevant (e.g. crystallization agents, water molecules, or alternative conformations). Docking with such raw structures may yield distorted conformations or even prevent the docking software from running properly.
In particular, the presence of alternate atom locations, solvent molecules, and missing hydrogens can drastically affect energy calculations or hinder accurate pose prediction in your docking simulations.
How to prepare your system in SAMSON
Thankfully, SAMSON simplifies this cleanup process with its built-in functionality:
- Go to Home > Prepare in the SAMSON menu.
- Check the following options:
- Remove alternate locations
- Remove water/ions/ligands (unless you are purposefully docking around a cofactor)
- Add hydrogens
Here’s what the preparation dialog looks like:
Extra tip: fixing incomplete structures
If your structure is missing residues or atoms in side chains, you can use the PDBFixer extension inside SAMSON—particularly helpful for proteins predicted from low-resolution models like AlphaFold.
Even better, PDBFixer can add hydrogens for specific pH values depending on your system’s environment.
Visualization for verification
Once your system is prepped, take a moment to visualize the secondary structures using:
- Visualization > Visual model > Ribbons
This step is helpful to quickly verify if you correctly removed the irrelevant parts of the structure and selected your ligand and receptor correctly.
Good to know
- The tutorial file provided in SAMSON already includes two pre-processed proteins (
2PTC_Eand2PTC_I), with water removed and hydrogens added. This is a great place to practice.
By ensuring that your system is clean and chemically correct, you not only save time during docking but also increase your chances of generating meaningful, interpretable results.
To learn more and follow the full tutorial on protein docking with Hex in SAMSON, visit the original documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.