One common challenge faced by structural biologists working with NMR-derived molecular structures is postprocessing. After initial structure generation with tools like CYANA, converting these NMR ensembles into high-quality, energy-minimized models suitable for publication or molecular design often requires manual setup of force fields, parameter files, and topology definitions—especially when the structures include non-standard residues or ligands.
The Molecular Restrainer Extension for SAMSON offers a streamlined solution. Leveraging the Universal Force Field (UFF) and NOE-derived distance restraints, it allows you to refine entire NMR ensembles directly—without the need for topology or parameter files.
Minimize NMR Ensembles in a Few Clicks
Here’s how easy it can be:
- Load your NMR structure into SAMSON. If it’s an ensemble, Molecular Restrainer can handle batch minimization out of the box.
- Open Molecular Restrainer through
Home > Apps > Biology > Molecular Restrainer, or find it using the Find everything… search bar. - Select the structure or the entire ensemble and click Set.
- Select the corresponding
.uplfile (upper-distance-limit distance restraints) you received from CYANA. - Ensure that the “Fix N- and C-termini” option is checked, so that any missing terminal atoms are automatically added.
- Click Start. You’re done.
The output includes minimized coordinates, energy profiles, and trajectory files. Because Molecular Restrainer matches restraints by atom names and residue IDs, it works best with standard hydrogen naming conventions. If your hydrogens are incorrectly named or incompletely defined along the trajectory, the restraints.log file will report which restraints couldn’t be applied—helpful for troubleshooting.
Why This Helps
Post-CYANA processing can often present roadblocks:
- Lack of force field parameters for modified amino acids or ligands,
- Missing hydrogen atoms in terminal regions, making traditional minimization fail,
- Manual verification of each structure or conformation, adding time and potential errors.
Molecular Restrainer addresses all three. It doesn’t require residue-specific parameters, automatically constructs hydrogen-based pseudoatoms for NOE restraint application, and allows you to apply the same processing across an entire ensemble. This is particularly useful for depositing conformationally-rich models to the PDB or using them directly in downstream analyses like ligand docking.
For an added layer of insight, Molecular Restrainer also provides a live visualization of restraint satisfaction. As the system minimizes, you’ll see the restraints displayed as bonds colored according to energy—green for satisfied, red for unsatisfied—which helps with debugging or presentation.
This approach can save hours for structural biologists handling large ensembles or structures with non-standard components—without having to dive into custom scripting or parameter tuning.
To explore the full setup and options, refer to the original documentation: https://documentation.samson-connect.net/tutorials/molecular-restrainer/molecular-restrainer/
SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON at https://www.samson-connect.net.