A Quick Way to Minimize Entire NMR Ensembles at Once in SAMSON

Working with NMR-derived molecular structures often means managing ensembles of conformations. But what if you need to quickly energy-minimize all conformations in one go—without messing with topology files or writing scripts?

The Molecular Restrainer extension in SAMSON provides a fast solution: integrated batch minimization for complete NMR ensembles with minimal setup. If you’re processing CYANA outputs or prepping models for PDB submission or further design tasks, this can save a lot of manual work.

Why batch minimization is useful

NMR structure determination often results in an ensemble of models representing possible conformations. While these are experimentally derived, they may still carry strain or exhibit bond geometry distortions, especially in ligands or non-standard residues. Minimizing just the first conformation might not be enough when your analysis or downstream workflows depend on the entire set being in a realistic energy well.

Traditionally, minimizing whole ensembles requires either writing code or applying tools that need force field customizations. That’s where the Molecular Restrainer comes in: it handles this automatically with support for standard and non-standard residues, no custom topology files required.

How to minimize a full NMR ensemble in SAMSON

Here’s a step-by-step walk-through of how batch minimization works using the Molecular Restrainer app in SAMSON.

  1. Load your NMR ensemble (including all conformations) into SAMSON. Each conformation appears as a point in a path or trajectory.
  2. Open the Molecular Restrainer from Home > Apps > Biology > Molecular Restrainer or by using Find everything….
  3. Click Set to define the ensemble for minimization. If nothing is selected, SAMSON will use the entire document, including paths and structures.
  4. Select your NOE-derived upper-distance-limit restraints file (e.g., a .upl file from CYANA).
  5. Click Start.

Running minimization - progress log

The app runs the minimization across all conformations. You can follow the progress in a live log. If needed, you can stop midway and still retain structures that were already processed.

Output files per conformation

The output folder contains detailed results including:

  • input.pdb – the original structure
  • minimized.pdb – the result
  • energy.csv – iteration-wise energy profile
  • restraints.log – a log of restraints that weren’t applied
  • minimized_path.pdb – if applicable, a continuous trajectory of minimized conformations

The minimized ensemble is ready for visualization, analysis, or further modeling steps such as docking or binding affinity estimation.

When to use this workflow

This batch minimization approach is particularly handy when:

  • Submitting models to PDB, which expects structures to meet geometry standards
  • Designing ligands or non-standard residues based on NMR data
  • Simplifying the post-processing of CYANA outputs
  • Running ensemble simulations where each member should start in an energetically minimized state

Final thoughts

Batch minimization can help make NMR ensembles more robust and consistent. Easier post-processing means faster workflows and fewer bottlenecks when transitioning from data to design or publication.

For full technical details and available options (including restraint weighting or stopping criteria), check the official documentation page.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can download SAMSON here.

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