If you’ve worked with NMR-derived structures, you probably know how tricky it can be to prepare them for deposition or modeling workflows. Especially when your system contains non-standard residues or ligands, setting up topology and force-field files often turns into a long detour from your real scientific goals.
Fortunately, there’s a way to skip all of that. Molecular Restrainer, a SAMSON Extension developed in collaboration between the Orts Group at the University of Vienna and OneAngstrom, lets you perform energy minimization of NMR-derived ensembles without custom parameter files. It uses the Universal Force Field (UFF) in combination with NOE-based distance restraints – and everything runs inside the SAMSON platform.
What Problem Does It Solve?
If you’ve ever gone from a CYANA output to trying to get a minimized structure suitable for the Protein Data Bank (PDB) or downstream analysis, you know it typically involves many steps including structure validation, adding missing atoms, preparing inputs for a force field, and testing if restraints are maintained.
Molecular Restrainer automates this entire pipeline, and does so without requiring topology or force-field parameter files.
What You Need
- SAMSON 2024 or newer
- The Molecular Restrainer extension (available here)
- The FIRE optimizer
- Your NMR ensemble in PDB format
- The corresponding CYANA-generated
.uplfile with distance restraints
How It Works
The process is simple. After launching SAMSON and opening the Molecular Restrainer app, you just:
- Load your NMR ensemble
- Select the structure or path (e.g. all conformations) to refine
- Load your
.uplfile (NOE-based restraints) - Press Start
The system combines UFF terms with the distance restraints and performs minimization using the FIRE optimizer. You don’t have to tune parameters unless you want to. The extension includes a fully-featured setup to control weights and convergence criteria, but the default values usually work out of the box.
Ensemble-Wide Minimization
Molecular Restrainer handles paths (i.e., ensembles of conformations) as part of its interface. If you load an NMR ensemble with multiple models, each can be minimized in batch – producing a trajectory of minimized conformations and logs for each.
Struggling With Missing Atoms?
The extension expects input structures to be complete, but includes a helpful option: “Fix N- and C-termini”, which can add missing N-terminal or C-terminal atoms for standard residues. This is especially useful for structures generated outside of standard modeling pipelines.
Still unsure whether your structure is complete? The tool also directs users to additional validation steps, though most clean NMR outputs should work by default.
What You Get
Once a minimization run is complete, a timestamped folder is created with the following files per conformation:
input.pdb– the original structureminimized.pdborstopped.pdbenergy.csv– energies per iteration
…plus logs and, if applicable, a combined minimized_path.pdb trajectory.
Why It’s Useful
This extension speeds up NMR refinement significantly, replacing multi-step protocols with a few clicks. If you routinely prepare structures for PDB deposition or docking, it may save hours of manual setup – and reduce the chance of mismatched atom names or broken restraints.
Learn more and explore additional features in the full documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at https://www.samson-connect.net.