Streamlined Postprocessing of NMR Structures with the Molecular Restrainer: A Universal Tool for High-Quality Protein–Ligand Models and Non-Standard Amino Acid Residues

TL;DR

A new tool called the Molecular Restrainer improves the quality of NMR-derived protein-ligand structures for publication and PDB deposition.

Contribution

A universal, automated postprocessing tool for NMR structures that eliminates the need for manual force field parameter creation.

Findings

The Molecular Restrainer significantly improves the quality of NMR-derived structures compared to CYANA outputs.

The tool can process any molecule or complex without requiring custom force field parameters or topology files.

Abstract

We present a molecular restrainer tool capable of energy-minimizing NMR-derived structures using the universal force field (UFF) and NOE-derived distance restraints. The implementation is a part of SAMSON (version 2024 and newer), an integrative molecular design platform. The strength of our tool lies in its ability to swiftly process any molecule and molecular complex without the need to create force field parameters and topology files. We show, using examples, that the quality of these refined structures is significantly improved compared to the starting structures derived by CYANA. Currently, the implementation is targeted toward the postprocessing of structures derived by the software CYANA but can easily be adapted to other molecular restraint formats. This tool enables the generation of publication-ready protein–ligand complex structures for PDB deposition, requiring minimal additional effort beyond the initial NMR structure calculation.

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