Lysozyme revisited: evaluating models of a reference protein in structural biology.
The study found no correlation between R_free and R_merge for lysozyme structures, indicating potential issues with structure quality in the Protein Data Bank.
Where it sits
this study against the rest of the p21 (p021) corpusSummary and findings
The study evaluated over 1200 crystal structures of hen egg-white lysozyme (HEWL) in the Protein Data Bank. It was found that there is no correlation between R_free and R_merge for 136 near-atomic-resolution lysozyme structures. The authors propose that inadequately refined structures be flagged in the PDB to prevent misuse in data analyses.
Abstract
We have evaluated the quality of over 1200 crystal structures of hen egg-white lysozyme (HEWL) deposited in the Protein Data Bank (PDB). These structures, collected over nearly 50 years, vary in quality, despite all representing essentially the same small enzyme consisting of 129 amino acid residues. Some of the entries originated from studies of the binding of small-molecule ligands to HEWL, whereas the majority of deposits represent the outcomes of tests of new experimental approaches to crystallization and data collection and/or evaluations of new computational protocols. We found no correlation between <i>R</i> <sub>free</sub>, which is a measure of structure quality, and <i>R</i> <sub>merge</sub>, an indicator of raw data quality, for 136 near-atomic-resolution lysozyme structures. We found out that many of the lysozyme structures deposited as a result of methodology evaluation are not fully or correctly refined. We, therefore, propose that such structures be appropriately flagged in the PDB with a CAVEAT record to prevent their inadvertent inclusion in large-scale data mining analyses or training sets for artificial intelligence methods.
Background
This paper addresses the quality of crystal structures of hen egg-white lysozyme (HEWL) in the Protein Data Bank, which has been a subject of research for nearly 50 years. Previous studies have indicated variability in the quality of these structures, despite them representing the same enzyme. Understanding the quality of these structures is crucial for their application in structural biology and computational methods.
Methods
The study involved evaluating over 1200 crystal structures of HEWL deposited in the Protein Data Bank. The authors specifically assessed 136 near-atomic-resolution structures to analyze the correlation between R_free and R_merge. The focus was on the quality of the structures and their refinement status.
Results
The primary finding was that there is no correlation between R_free and R_merge for the 136 near-atomic-resolution lysozyme structures evaluated. The study also highlighted that many structures resulting from methodology evaluations are inadequately refined.
Interpretation
These findings suggest that the quality of crystal structures in the PDB may not be as reliable as previously assumed. While the lack of correlation between R_free and R_merge is statistically significant, the clinical relevance of these findings is limited as they pertain to structural quality rather than direct biological outcomes. The proposal to flag inadequately refined structures could enhance data integrity but does not address the underlying issues of structure quality.
Key findings
- No correlation between R_free and R_merge for 136 near-atomic-resolution lysozyme structures.
- Many lysozyme structures from methodology evaluation are not fully or correctly refined.
- Proposed flagging of inadequately refined structures in the PDB with a CAVEAT record.
Limitations
- Evaluation based on existing PDB entries, not new experimental data.
- No clinical or biological outcomes assessed.
- Potential bias in structure selection not reported.