We are proud to announce an important milestone for PDB-Dev - the first 100 entries are released to the public. This achievement is a result of the continued collaboration among the PDB-Dev team, members of the wwPDB IHM task force, wwPDB leadership, RCSB PDB team members, and our pioneer depositors, who were the first to realize the importance of sharing the results of integrative structural biology investigations. The PDB-Dev project is funded by the United States National Science Foundation.
The first 100 entries also offer us a glimpse of the complex landscape of modern integrative modeling. While experimental models used with chemical cross-linking are a leading category, techniques such as three-dimensional electron microscopy (3DEM), small angle solution scattering (SAS), Forster resonance enery transfer (FRET), and others, together with powerful AI-based methods for the de novo structure prediction, give us more than 50(!) unique combinations of datasets used for integrative modeling (see figure below). Because integrative structures provide a unique opportunity to gain insights into how biomolecules function in conditions close to the native, many of these investigations are featured in journals such as Cell, Nature, Science, Proceedings of the National Academy of Sciences, and the Journal of Molecular Biology.
We designed PDB-Dev according to the FAIR guiding principles to make the integrative structures of biomolecules Findable, Accessible, Interoperable, and Reusable, and with the your help, we will continue to improve it and provide better archiving and structure validation services to our users.
Combinations of datasets used for integrative modeling studies and their frequencies in PDB-Dev entries
For a long time, the primary sources of starting structures for integrative modeling were experimental structures from the Protein Data Bank or computational models generated using various comparative modeling approaches. The recent machine learning revolution has led to the development of modeling methods like AlphaFold2 and RoseTTAFold, and also brought a whole new universe of high-quality predicted structures of proteins. More than 200 million predicted structures of individual proteins and complexes are now available to researchers across multiple databases. Now these structures are finally making their way into integrative modeling.
In PDBDEV_00000141, Noone et. al., report a structure of pentraxin protein PTX3, a member of a family of soluble pattern recognition molecules that form an important part of innate immunity, where they facilitate the response to infections and damage by triggering processes such as inflammation. The complete structure of PTX3 was built by integrative modeling using three-dimensional electron microscopy map, mass spectrometry data, and AlphaFold-based starting models.
The validation report consists of four categories: (i) model composition, (ii) data quality assessments, (iii) model quality assessments, and (iv) fit to data used to build the model. At present, data quality assessments and fit to data used to build the models are evaluated for models built using Small Angle Scattering (SAS) data based on the guidelines published by the wwPDB SAS validation task force.
Validation of integrative structures is a work in progress and additional criteria for validating models based on different experimental methods (such as FRET, chemical crosslinking, 3DEM) will be incorporated in subsequent versions of the validation report.
Please reach out us via email if you have any questions or comments.
We have updated the embargo (HOLD) policy for structures deposited to PDB-Dev. Following wwPDB policies, entries can be placed on hold for a maximum period of one year from the date of deposition. If an entry remains unreleased at the end of the hold period, it must either be released or withdrawn. All unreleased entries that have been on HOLD for more than a year have been released by June 24th, 2022. The updated embargo policy is effective from July 1st 2022.
We have developed a new Deposition and Data Harvesting System that provides a web interface for depositors to assemble all the information required for archiving integrative structures in PDB-Dev, generate a compliant mmCIF file, and deposit the structure to PDB-Dev. This includes the submission of integrative structures, associated spatial restraints and starting models used, modeling protocols and metadata information (citations, authors, software, data in external repositories, reference sequence information etc.).
The system provides an automated mechanism for collecting diverse and heterogeneous types of integrative structures and restraint data. It has been developed using the DERIVA scientific asset management platform and is based on the definitions in the IHM-dictionary and the parent PDBx/mmCIF dictionary.
A User Guide has been created with documentation regarding creating accounts and submitting structures.
The old deposition system that had rudimentary file upload functionality, has been deprecated as of June 3rd, 2022.
Recent updates to PDB-Dev, including the development of a new data harvesting system, have been published in Acta Crystallographica Section D: Vallat B et al., New sytem for archiving integrative structures, Acta Cryst. 2021; D77: 1486-1496. doi:10.1107/S2059798321010871
Recently, the PDB-Dev team participated in the BioExcel webinar series. The webinar presentation was titled "PDB-Dev: A prototype system for archiving integrative structures". The recorded version of the webinar is available on youtube.
3D visualization of structures using Molstar is now available on PDB-Dev. Structures in PDB-Dev can be directly visualized from the respective entry pages. Molstar can visualize atomic as well as multi-scale structures.
Integrative structures can also be visualized online using the Molstar viewer.
Molstar is an open collaboration started by PDBe and RCSB PDB to provide a technology stack for data delivery and analysis tools of macromolecules.
The PDB-Dev web interface has been revamped to provide dynamic, responsive and mobile-friendly web pages. The newly designed website has been made possible due to an overhaul of our backend infrastructure.
The PDB-Dev website now includes a new service that facilitates search and retrieval of integrative structures archived in PDB-Dev. Simple search using macromolecular names (e.g., nuclear pore complex), entry identifiers (e.g., PDBDEV_00000012), experimental methods used (e.g., NMR, 3DEM, CX-MS), author names (e.g., Sali), software used (e.g., IMP, HADDOCK, ROSETTA), and several other keywords are now supported. Search results can be downloaded as CSV or EXCEL files.
We have also added individual entry pages that provide a summary of the structure (title, description, authors) along with other details regarding the citation, software, input data, and links to related resources and downloading the structure.
In March 2019, a satellite workshop titled “Working towards federating structural models and data” was held at the Biophysical Society Annual meeting in Baltimore, Maryland to assess current progress and discuss further requirements for archiving integrative structures. The primary goal of the workshop was to bring together experts from different scientific communities contributing to integrative structural biology and build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validation of integrative structures. A whitepaper summarizing the outcomes of the workshop was recently published in the journal Structure.
The integrative structures can be downloaded as text files (use right click + save as) and opened on ChimeraX using the "format ihm" command line option along with the complete path to the downloaded file:
open path/to/myfile.cif format ihm
Alternately, the following command can be used to directly visualize an entry from PDB-Dev, eg: PDBDEV_00000010.
open 10 from pdbdev ignoreCache true
The PDB-Dev entry files have been recently updated to comply with updates in the IHM dictionary.
Older files downloaded from PDB-Dev will not be supported on the latest ChimeraX. Similarly, the new PDB-Dev files will not be supported on older versions of ChimeraX.
Please download a fresh copy of the file from PDB-Dev and/or clear the ChimeraX cached IHM files (delete ~/Downloads/ChimeraX/PDBDev) for visualizing the updated files with the latest ChimeraX.