Protein NMR Structures Refined with Rosetta Have Higher Accuracy Relative to Corresponding X-ray Crystal Structures
By Binchen Mao, R. Tejero, David Baker, Gaetano T. Montelione. 2014
69 citations recorded by the source corpus.
We have found that refinement of protein NMR structures using Rosetta with experimental NMR restraints yields more accurate protein NMR structures than those that have been deposited in the PDB using standard refinement protocols. Using 40 pairs of NMR and X-ray crystal structures determined by the Northeast Structural Genomics Consortium, for proteins ranging in size from 5 – 22 kDa, restrained-Rosetta refined structures fit better to the raw experimental data, are in better agreement with their X-ray counterparts, and have better phasing power compared to conventionally determined NMR structures. For 38 proteins for which NMR ensembles were available and which had similar structures in solution and in the crystal, all of the restrained-Rosetta refined NMR structures were sufficiently accurate to be used for solving the corresponding X-ray crystal structures by molecular replacement. The protocol for restrained refinement of protein NMR structures was also compared with restrained CS-Rosetta calculations. For proteins smaller than 10 kDa, restrained CS-Rosetta, starting from extended conformations, provides slightly more accurate structures, while for proteins in the size range of 10 – 25 kDa the less cpu intensive restrained-Rosetta refinement protocols provided more accurate structures. The restrained-Rosetta protocols described here can improve the accuracy of protein NMR structures, and should find broad and general for studies of protein structure and function.
Subfields: Materials Chemistry, Molecular Biology
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Materials Chemistry
- Gaetano T. Montelione
- Yuanpeng Janet Huang
- Santrupti Nerli
- David E. Shaw
- Paul Robustelli
- R. Tejero
- T. Ramelot
- Nikolaos G. Sgourakis
In Molecular Biology
- Santrupti Nerli
- Nikolaos G. Sgourakis
- Gaetano T. Montelione
- Yuanpeng Janet Huang
- R. Tejero
- T. Ramelot
- Andrew C. McShan
- David E. Shaw
Citations in the corpus
- Tertiary alphabet for the observable protein structural universe (2016, methodology): “For the combined Rosetta-TERMs design procedure, we limited the amino acids that Rosetta could use at position r to the smallest set that accounted for at least 80% cumulative probability according to TERM-based self-energy (i.e., f a 1 , ...”
- Developing a molecular dynamics force field for both folded and disordered protein states (2018, methodology): “We found that a99SB*-ILDN/TIP3P yielded both the most stable simulations of the proteins in the set by Huang et al. (6) and the closest agreement with experimental chemical shifts and NOEs in the dataset by Mao et al. (35).”
- AlphaFold Models of Small Proteins Rival the Accuracy of Solution NMR Structures (2022, methodology): “Included in this analysis are the corresponding NMR structures refined using a NMR-data-restrained Rosetta modeling protocol (Mao et al., 2014).”
- Chemical shift-based methods in NMR structure determination (2018, methodology): “Finally, the full set of assigned NMR restraints and evolutionary couplings are used to refine the preliminary CYANA models using Rosetta’s all-atom energy function [134].”
- Protein structure determination by combining sparse NMR data with evolutionary couplings (2015, unknown): “The resulting output file final.upl is then used for restrained Rosetta refinement, as described elsewhere 2 .”