A public database of macromolecular diffraction experiments

Abstract

The low reproducibility of published experimental results in many scientific disciplines has recently garnered negative attention in scientific journals and the general media. Public transparency, including the availability of `raw' experimental data, will help to address growing concerns regarding scientific integrity. Macromolecular X-ray crystallography has led the way in requiring the public dissemination of atomic coordinates and a wealth of experimental data, making the field one of the most reproducible in the biological sciences. However, there remains no mandate for public disclosure of the original diffraction data. The Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) has been developed to archive raw data from diffraction experiments and, equally importantly, to provide related metadata. Currently, the database of our resource contains data from 2920 macromolecular diffraction experiments (5767 data sets), accounting for around 3% of all depositions in the Protein Data Bank (PDB), with their corresponding partially curated metadata. IRRMC utilizes distributed storage implemented using a federated architecture of many independent storage servers, which provides both scalability and sustainability. The resource, which is accessibleviathe web portal at http://www.proteindiffraction.org, can be searched using various criteria. All data are available for unrestricted access and download. The resource serves as a proof of concept and demonstrates the feasibility of archiving raw diffraction data and associated metadata from X-ray crystallographic studies of biological macromolecules. The goal is to expand this resource and include data sets that failed to yield X-ray structures in order to facilitate collaborative efforts that will improve protein structure-determination methods and to ensure the availability of `orphan' data left behind for various reasons by individual investigators and/or extinct structural genomics projects.

Substrate specificity and reaction mechanism of human prolidase

“…Coordinates and structure factors have been deposited in the Protein Data Bank with accession number 5M4G for HsProl-Mn, 4M4J, for HsProl-Na-GlyPro, 5M4L for HsProl-Mg-LeuPro, and 5M4Q for HsProl-Mn-Pro, respectively. All original diffraction images are available via the IRRMC [71] with DOIs https://doi.org/10.18430/M35M4G, https://doi.org/10.18430/M35M4J, https://doi.org/10.18430/ M35M4L and https://doi.org/10.18430/M35M4Q, respectively.…”

Structural basis for prolidase deficiency disease mechanisms

“…In this variant, Tyr241 is pushed away by Asp278 and hence this source of stabilization is lost. Interestingly, the ligand-binding residue His255 in subunit B is found 29 A from the ligand position while in subunit A it remains in the usual position. However, it does exhibit very high ADP values (~90 A 2 ) and is just barely traceable.…”

“…All refined coordinates and corresponding structure factor amplitudes have been deposited in the protein data bank [28] with accession numbers 5MBY, 5MBZ, 5MC0, 5MC1, 5MC2, 5MC3, 5MC4, 5MC5, and 6H2P, 6H2Q. The raw diffraction images for both high resolution and low energy (anomalous) data sets were deposited in the Integrated Resource for Reproducibility in Macromolecular Crystallography (IRRMC) [29] with the accession codes linked to the respective PDB entries.…”

Crystallography and Databases

“…These include: establishment of university research data archives e.g. at the University of Manchester Library (University of Manchester 2013); centralized initiatives at ESRF (European Synchrotron Radiation Facility, 2016) and Zenodo (OpenAIRE 2017) in Europe; SBGrid Data Bank (https:// data.sbgrid.org/; Meyer et al 2016) and the BD2K (Big Data to Knowledge) initiative (Grabowski et al 2016) in the USA. These extend the exemplary approaches of data archiving at the neutron facilities ISIS (Science & Technology Facilities Council 2011) and Institut Laue Langevin (Institut Laue Langevin 2011), and at Store.…”