The accuracy of NMR protein structures in the Protein Data Bank

Fowler, Nicholas; Sljoka, Adnan; Williamson, Michael P.

doi:10.1016/j.str.2021.07.001

Cited by 12 publications

(24 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two reviews comparing NMR and crystal structures (Andrec et al, 2007;Billeter, 1992) have concluded that NMR structures have the same fold as corresponding crystal structures but are, on average, of lower quality. Our own analysis using ANSURR (Fowler et al, 2020(Fowler et al, , 2021 reached the same conclusion. An interesting point made by Andrec et al (2007) is that the precision of the NMR ensemble is tighter than the average distance between the NMR ensemble and the crystal structure; that is, that the most obvious measure of the ''error'' of the NMR structures is misleadingly small-not only are NMR structures of low quality, but the error attached to them is unreliable.…”

Section: Discussionsupporting

confidence: 71%

“…We therefore felt that removing any ligands from NMR structures was the fairest comparison. We showed previously (Fowler et al, 2021) that ligands can cause changes in computed flexibility, but that the overall effect on ANSURR score is small: including ligands to compute flexibility for a set of 162 NMR ensembles led to a mean change in ANSURR score of only 1. Secondary structure was classified using DSSP v2.0.4 (Touw et al, 2015).…”

Section: Acknowledgmentsmentioning

confidence: 91%

“…In contrast, b-sheets can adopt a wider range of local geometries, making it more challenging to correctly resolve hydrogen bonds. We have noted this effect before (Fowler et al, 2021) and found that NMR structures often lack hydrogen bonds in b-sheets.…”

Section: Target T1029mentioning

confidence: 91%

“…The increased accuracy largely stemmed from AF2 models having more extensive hydrogen-bond networks than NMR structures, which results in them being more rigid overall, giving them a higher ANSURR RMSD score. We have noted previously (Fowler et al, 2021) that NMR structures tend to be too floppy and that increasing the rigidity of the NMR structure by the addition of hydrogen bonds generally improves its ANSURR score. The locations of the hydrogen bonds do of course have to be correct, and AF2 provides accurate predictions of hydrogen-bond locations (Jumper et al, 2021).…”

Section: Target T1029mentioning

confidence: 99%

See 3 more Smart Citations

The accuracy of protein structures in solution determined by AlphaFold and NMR

Fowler

Williamson

2022

Structure

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 71%

Section: Acknowledgmentsmentioning

confidence: 91%

Section: Target T1029mentioning

confidence: 91%

Section: Target T1029mentioning

confidence: 99%

See 2 more Smart Citations

The accuracy of protein structures in solution determined by AlphaFold and NMR

Fowler

Williamson

2022

Structure

Self Cite

View full text Add to dashboard Cite

“…A recent study reported that many NMR structures have surface loops that are often underrestrained and too floppy 33 . This observation is consistent with our finding that the cores of NMR structures solved with few distance restraints are typically too small.…”

Section: Discussionmentioning

confidence: 99%

Core packing of well-defined x-ray and NMR structures is the same

Grigas¹,

Liu²,

Regan³

et al. 2022

Preprint

View full text Add to dashboard Cite

Numerous studies have investigated the differences and similarities between protein structures determined by solution NMR spectroscopy and those determined by x-ray crystallography. A fundamental question is whether any observed differences are due to differing methodologies, or to differences in the behavior of proteins in solution versus in the crystalline state. Here, we compare the properties of the hydrophobic cores of high-resolution protein crystal structures and those in NMR structures, determined using increasing numbers and types of restraints. Prior studies have reported that many NMR structures have denser cores compared to those of high-resolution x-ray crystal structures. Our current work investigates this result in more detail, and finds that these NMR structures tend to violate basic features of protein stereochemistry, such as small non-bonded atomic overlaps and few Ramachandran and side chain dihedral angle outliers. We find that NMR structures solved with more restraints, and which do not significantly violate stereochemistry, have hydrophobic cores that have a similar size and packing fraction as their counterparts determined by x-ray crystallography at high-resolution. These results lead us to conclude that, at least regarding the core packing properties, high-quality structures determined by NMR and x-ray crystallography are the same, and the differences reported earlier are most likely a consequence of methodology, rather than fundamental differences between the protein in the two different environments.Significance: Dense packing of hydrophobic residues is key to protein structure and stability. Previously, it has been noted that structures solved by NMR spectroscopy have denser cores than xray crystal structures. Here, we calculate the core size and packing fraction of NMR structures with experimental restraints in the PDB. Their cores are typically smaller, but denser. However, NMR structures with accurate stereochemistry possess core packing properties that are nearly identical to high-resolution x-ray crystal structures.

show abstract

Core packing of well‐defined X‐ray and NMR structures is the same

et al. 2022

View full text Add to dashboard Cite

Numerous studies have investigated the differences and similarities between protein structures determined by solution NMR spectroscopy and those determined by X‐ray crystallography. A fundamental question is whether any observed differences are due to differing methodologies or to differences in the behavior of proteins in solution versus in the crystalline state. Here, we compare the properties of the hydrophobic cores of high‐resolution protein crystal structures and those in NMR structures, determined using increasing numbers and types of restraints. Prior studies have reported that many NMR structures have denser cores compared with those of high‐resolution X‐ray crystal structures. Our current work investigates this result in more detail and finds that these NMR structures tend to violate basic features of protein stereochemistry, such as small non‐bonded atomic overlaps and few Ramachandran and sidechain dihedral angle outliers. We find that NMR structures solved with more restraints, and which do not significantly violate stereochemistry, have hydrophobic cores that have a similar size and packing fraction as their counterparts determined by X‐ray crystallography at high resolution. These results lead us to conclude that, at least regarding the core packing properties, high‐quality structures determined by NMR and X‐ray crystallography are the same, and the differences reported earlier are most likely a consequence of methodology, rather than fundamental differences between the protein in the two different environments.

show abstract

The accuracy of NMR protein structures in the Protein Data Bank

Cited by 12 publications

References 43 publications

The accuracy of protein structures in solution determined by AlphaFold and NMR

The accuracy of protein structures in solution determined by AlphaFold and NMR

Core packing of well-defined x-ray and NMR structures is the same

Core packing of well‐defined X‐ray and NMR structures is the same

Contact Info

Product

Resources

About