Rxivist logo

Integrative protein modeling in RosettaNMR from sparse paramagnetic restraints

By Georg Kuenze, Richard Bonneau, Julia Koehler Leman, Jens Meiler

Posted 03 Apr 2019
bioRxiv DOI: 10.1101/597872 (published DOI: 10.1016/j.str.2019.08.012)

Computational methods to predict protein structure from nuclear magnetic resonance (NMR) restraints that only require assignment of backbone signals hold great potential to study larger proteins and complexes. Additionally, computational methods designed to work with sparse data add atomic detail that is missing in the experimental restraints, allowing application to systems that are difficult to investigate. While specific frameworks in the Rosetta macromolecular modeling suite support the use of certain NMR restraint types, use of all commonly measured restraint types together is precluded. Here, we introduce a comprehensive framework into Rosetta that reconciles CS-Rosetta, PCS-Rosetta and RosettaNMR into a single framework, that, in addition to backbone chemical shifts and nuclear Overhauser effect distance restraints, leverages NMR restraints derived from paramagnetic labeling. Specifically, RosettaNMR incorporates pseudocontact shifts, residual dipolar couplings, and paramagnetic relaxation enhancements, measured at multiple tagging sites. We further showcase the generality of RosettaNMR for various modeling challenges and benchmark it on 28 structure prediction cases, eight symmetric assemblies, two protein-protein and three protein-ligand docking examples. Paramagnetic restraints generated more accurate models for 85% of the benchmark proteins and, when combined with chemical shifts, sampled high-accuracy models (≤ 2Å) in 50% of the cases.

Download data

  • Downloaded 314 times
  • Download rankings, all-time:
    • Site-wide: 48,502 out of 85,215
    • In biophysics: 2,008 out of 3,671
  • Year to date:
    • Site-wide: 49,597 out of 85,215
  • Since beginning of last month:
    • Site-wide: 51,785 out of 85,215

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)