Annotation and Curation of the Protein Data Bank

The Protein Data Bank (PDB) is the worldwide repository for experimentally determined 3D structures of biological macromolecules. Established in 1971 with just seven structures, it presently includes more than 56,000 entries. To maintain the highest standards in curation and processing, the members of the worldwide Protein Data Bank (wwPDB) collaborate in data annotation and the development of procedures, tools, and resources. Annotation-related issues, particularly those impacted by new developments
in structural biology, are critically reviewed at in-person and virtual meetings regularly and frequently. Comprehensive documentation of the procedures, formats, and related data dictionaries used in data annotation are available at the wwPDB website(www.wwpdb.org).

Mindful of the impact that changes in annotation procedures or data format may have on users, changes are carefully managed and communicated in a timely fashion. In cases involving complex scientific or policy issues, input is sought from advisory committees, standing task forces, experimental method developers, and community experts. This is exemplified by creation of the recently-released version of the PDB archive which updates and further standardizes database references, small molecule chemistry, biological assemblies, and active sites

Using structural analysis In Silico to assess the impact of missense variants in MEN1

Despite the rapid expansion in recent years of databases reporting either benign or pathogenic genetic variations, the interpretation of novel missense variants remains challenging, particularly for clinical or genetic testing laboratories where functional analysis is often unfeasible. Previous studies have shown that thermodynamic analysis of protein structure in silico can discriminate between groups of benign and pathogenic missense variants. However, although structures exist for many human disease‒associated proteins, such analysis remains largely unexploited in clinical laboratories. Here, we analyzed the predicted effect of 338 known missense variants on the structure of menin, the MEN1 gene product. Results provided strong discrimination between pathogenic and benign variants, with a threshold of >4 kcal/mol for the predicted change in stability, providing a strong indicator of pathogenicity. Subsequent analysis of seven novel missense variants identified during clinical testing of patients with MEN1 showed that all seven were predicted to destabilize menin by >4 kcal/mol. We conclude that structural analysis provides a useful tool in understanding the effect of missense variants in MEN1 and that integration of proteomic with genomic data could potentially contribute to the classification of novel variants in this disease.This article is freely available via Open Access. Click on the Publisher URL to access the full-text.Open Acces

The NMR restraints grid at BMRB for 5,266 protein and nucleic acid PDB entries

Several pilot experiments have indicated that improvements in older NMR structures can be expected by applying modern software and new protocols (Nabuurs et al. in Proteins 55:483–186, 2004; Nederveen et al. in Proteins 59:662–672, 2005; Saccenti and Rosato in J Biomol NMR 40:251–261, 2008). A recent large scale X-ray study also has shown that modern software can significantly improve the quality of X-ray structures that were deposited more than a few years ago (Joosten et al. in J. Appl Crystallogr 42:376–384, 2009; Sanderson in Nature 459:1038–1039, 2009). Recalculation of three-dimensional coordinates requires that the original experimental data are available and complete, and are semantically and syntactically correct, or are at least correct enough to be reconstructed. For multiple reasons, including a lack of standards, the heterogeneity of the experimental data and the many NMR experiment types, it has not been practical to parse a large proportion of the originally deposited NMR experimental data files related to protein NMR structures. This has made impractical the automatic recalculation, and thus improvement, of the three dimensional coordinates of these structures. We here describe a large-scale international collaborative effort to make all deposited experimental NMR data semantically and syntactically homogeneous, and thus useful for further research. A total of 4,014 out of 5,266 entries were ‘cleaned’ in this process. For 1,387 entries, human intervention was needed. Continuous efforts in automating the parsing of both old, and newly deposited files is steadily decreasing this fraction. The cleaned data files are available from the NMR restraints grid at http://restraintsgrid.bmrb.wisc.edu

2027-09-26 - Worldwide Protein Data Bank - CoreTrustSeal Requirements 2023-2025

CoreTrustSeal certificatio

2024-05-07 - Worldwide Protein Data Bank - CoreTrustSeal Requirements 2020-2022

CoreTrustSeal certificatio