Refining NMR Structures Without Topology Files: A Fast Approach Using SAMSON

For molecular modelers working with NMR-derived structures, one of the recurring challenges is refining these structures without spending hours generating topology or parameter files — especially when dealing with non-standard residues or ligand-bound proteins. If you’ve ever struggled with converting a .upl file into something usable, or got stuck on missing atoms or alternate locations, you’re not alone!

Fortunately, there’s an efficient solution built directly into the SAMSON platform: the Molecular Restrainer Extension. This blog post focuses on a key capability of this tool—the ability to refine your NMR ensembles using NOE-derived restraints and the Universal Force Field (UFF), without any custom topology or force field parameters.

Why This Matters

NMR ensembles are rich in structural data, but they often need energy minimization to become suitable for further modeling or deposition. Traditional refinement workflows can be time-consuming and may require specialized software or manual editing. SAMSON’s Molecular Restrainer streamlines this into a few clicks.

How It Works

The basic setup is simple:

  • Load your NMR ensemble into SAMSON.
  • Open the Molecular Restrainer from Home > Apps > Biology.
  • Set the structure or ensemble you’d like to minimize.
  • Load your .upl restraint file from CYANA.
  • Click Start. That’s it.

No need to generate custom topologies or worry about missing parameters. UFF handles a wide range of molecule types, from proteins with standard residues to ligand-protein complexes featuring entirely non-standard atoms.

Batch Minimization with One Click

Got a full ensemble to process? The Molecular Restrainer automatically treats multi-conformer input files as paths (trajectories). It can minimize all conformations in one go and produce a single minimized trajectory.

Output Files

Each run creates a timestamped results folder with several useful files per minimized conformation:

  • input.pdb
  • minimized.pdb or stopped.pdb
  • energy.csv (energy over iterations)
  • restraints.log (unmatched restraints)
  • output.log

You can also get minimized_path.pdb if your original file contained multiple conformations — very useful for analysis or visualization.

Built-In Restraint Visualization

What’s going on during the minimization? SAMSON displays the applied NOE restraints as dynamic bonds with real-time color coding: green means satisfied, while red indicates high-energy, unsatisfied restraints. You can update restraint visualization settings in the Inspector for greater control.

Molecular Restrainer - Minimizing

Tips

  • If any conformations in your ensemble have missing terminal atoms, enable the Fix N- and C-termini option before minimization.
  • Keep restraints consistent with atom naming in your input file to ensure proper mapping.
  • restraints.log helps identify where restraints couldn’t be applied, which is handy for troubleshooting.

To learn more about how the algorithm works under the hood or to review validation benchmarks, check out the detailed guide in the SAMSON 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 from https://www.samson-connect.net.

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