Creating a community resource for protein science

Abstract

In addition to being one of the early pioneers in protein crystallography, Carl Br€ and en made significant contributions to science education with his elegant and beautifully illustrated book Introduction to Protein Structure (Br€ and en and Tooze, New York: Garland, 1991). It is truly an honor to receive this award in their names. This award and the 40th anniversary of the Protein Data Bank (PDB; Berman et al., Structure 2012;20:391-396) have given me an opportunity to reflect on the various components that have contributed to building a resource for protein science and to try to quantify the impact of having PDB data openly available.

Protein–protein interactions: General trends in the relationship between binding affinity and interfacial buried surface area

“…Although this dataset contained only 10 homodimers and 9 heterodimers, the data nevertheless hinted at a direct relationship between the surface area buried upon complex formation and the strength of the interaction. Since these pioneering studies, the number of structures in the Protein Data Bank (PDB)12 has increased to almost 70,000 in 2011 13. Therefore, we now revisit this topic with more available structures, thermodynamic data, and a focus on heterodimers, which tend to be involved in essential cellular processes such as signal transduction and histone modification.…”

Trendspotting in the Protein Data Bank

“…(A) Depositions per year are shown in black and total released entries available in gray on a logarithmic scale. Reprinted from Berman [46] with permission from Wiley; (B) growth of depositions from X‐ray crystallography. Depositions per year are shown in black and total released entries available in light gray; (C) growth in depositions from NMR.…”

“…This plot shows that while the use of home sources for X‐ray structure determination has remained roughly constant, the use of synchrotron sources has increased rapidly. Reprinted from Berman [46] with permission from Wiley; (B) use of SAD (in black) and MAD (in gray) phasing in PDB entries deposited per year. After an initial growth in MAD phasing, SAD phasing has become more widely used.…”

“…The large increase shown in 1984 was due to the release of the tomato bushy stunt virus 2tbv [47]; (B) the number of PDB entries, total related polymer chains, and protein sequences (with 50% redundancy as calculated using blastclust [48]) available in the archive each year; (C) the number of unique non‐polymer ligands released each year (a single entry may have several ligands). There are three notable peaks: 73 structures with an inhibitor/antibiotic were released in 1994, the majority of which are thrombin inhibitors and renin inhibitors; 130 structures in 2006, the majority of which are thrombin inhibitors and other protease inhibitors; and 140 structures in 2011, the majority of which are protease inhibitors, including caspase inhibitors; (B and C) reprinted from Berman [46] with permission from Wiley; (D) the number of peptide‐like inhibitor/antibiotic entries released per year.…”

VS-APPLE: A Virtual Screening Algorithm Using Promiscuous Protein–Ligand Complexes

“…Indeed, the Protein Data Bank (PDB) contains the structures of more than 75 complexes of ligand-binding HIV reverse transcriptase and 260 complexes of ligand-binding HIV protease. 5 Figure 1 illustrates the promiscuous binding of HIV reverse transcriptase to several different ligands. Other compounds bound to this protein should share common features with these distributed ligands, namely, their structures, chemical properties, and binding positions on the protein surface.…”