The impact of structural genomics: the first quindecennial

Abstract

The period 2000-2015 brought the advent of high-throughput approaches to protein structure determination. With the overall funding on the order of $2 billion (in 2010 dollars), the structural genomics (SG) consortia established worldwide have developed pipelines for target selection, protein production, sample preparation, crystallization, and structure determination by X-ray crystallography and NMR. These efforts resulted in the determination of over 13,500 protein structures, mostly from unique protein families, and increased the structural coverage of the expanding protein universe. SG programs contributed over 4400 publications to the scientific literature. The NIH-funded Protein Structure Initiatives alone have produced over 2000 scientific publications, which to date have attracted more than 93,000 citations. Software and database developments that were necessary to handle high-throughput structure determination workflows have led to structures of better quality and improved integrity of the associated data. Organized and accessible data have a positive impact on the reproducibility of scientific experiments. Most of the experimental data generated by the SG centers are freely available to the community and has been utilized by scientists in various fields of research. SG projects have created, improved, streamlined, and validated many protocols for protein production and crystallization, data collection, and functional analysis, significantly benefiting biological and biomedical research.

Keywords: NMR; Protein crystallography; Structural genomics.

Fig. 1

The structural output of SG programs. The vertical axis represents the number of structures deposited to the PDB by SG programs worldwide. Structures were assigned to a particular SG program based on the contents of mmCIF files (field _pdbx_SG_project) with manual curation in the PDB as of December 31, 2015.

Fig. 2

Percentage of PDB structures with primary citation “to be published” in the period 2000–2015 in function of the year of deposition for the PSI deposits (red line) and traditional (non-SG) deposits (blue line).

Fig. 3

Number of publications produced by the PSI, based on data from the PSI Publications Portal database as of August, 24, 2015.

Fig. 4

The average number of citations received in 2014 by PSI paper, as a function of the year of publication.

Fig. 5

Distribution of the number of citations of PSI publications. The horizontal axis represents the number of citations, and the vertical axis represents number of publications with a given number of citations.

Fig. 6

The average number of missing data items (“NULLs”) for all PDB deposits using X-ray crystallography (including both traditional structural biology and SG) as a function of the year of deposition from 1972 to 2014 is shown in blue. The average number of NULLs in X-ray crystallography PDB files from the PSI initiative (2000–2014) is shown in red.

Fig. 7

Average R_free by resolution bin (with a width of 0.2 Å) for X-ray crystallography structures deposited to PDB from January 2001 to March 2015, divided into two groups by the number of missing data items (“NULLs”) in the PDB file. The means for “high-completion” deposits (20 NULLs or less) are shown in blue, and the means for “low-completion” deposits (50 or more NULLs) are shown in red.