If you’ve ever experienced strange docking results—ligands floating in space, distorted poses, or unrealistic interactions—it might not be a scoring function issue. In many cases, the problem originates from poorly prepared ligand structures. Whether your ligand library comes from a public database such as ZINC or was exported from your favorite sketching tool, these ligands often require one important step before docking: minimization.
Minimizing ligands helps ensure that the initial geometry makes sense before evaluating any molecular interactions. Here’s how to easily perform ligand minimization in SAMSON using the AutoDock Vina Extended Extension.
Why minimize ligands?
- Fix 2D structures: Public libraries often provide ligands in 2D formats (e.g., SDF), meaning atoms lie on a plane with unrealistic angles and bond lengths. Minimization can convert these into chemically reasonable 3D structures.
- Improve initial scores: Docking algorithms often assume a realistic starting conformation. Minimization avoids wasting search effort on already-invalid structures.
- Hydrogen placement: Minimization can help verify hydrogen positions or add missing hydrogens, particularly polar hydrogens necessary for calculating H-bonds.
How to minimize ligands in SAMSON
In the AutoDock Vina Extended interface in SAMSON, set up your system as usual—with receptors and a ligand or a ligand library. When you’re about to add your ligands, check the option to minimize them before docking:
Steps:
- In the Set ligand section, check either Single Ligand or Ligand Library.
- Click on the Minimize checkbox.
- Select a preset minimization strategy: you can choose based on the number of steps and convergence criteria.
- If your ligands lack hydrogens, check Add missing hydrogens. This is crucial for polar interaction detection.
During docking, ligands will be minimized before being scored, ensuring more reliable and realistic results.
Handling rotatable bonds wisely
Minimization considers geometry but does not freeze specific bonds. If you want to restrict bond rotations during docking (for instance, to maintain a ring conformation), you can lock specific bond types separately after minimization. Keep in mind that locked bonds remain rotatable during minimization—they are only fixed during docking.
Got multiple ligands?
When working with a ligand library, SAMSON applies minimization uniformly across all ligands. Whether you’re screening a dozen compounds or thousands, this step can dramatically improve your hit quality and reduce false positives in downstream analysis.
Conclusion
Performing ligand minimization prior to docking is a small step that can avoid major issues later. Whether you’re docking a single compound or running a virtual screen on a compound library, using the combined power of SAMSON’s intuitive interface and AutoDock Vina Extended ensures your structures are ready for reliable predictions.
To explore this workflow in more detail and follow step-by-step examples, visit the complete documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.