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PDB 50th Anniversary: celebrating the future of structural biology

In honor of the 50th anniversary of the Protein Data Bank, Nature Methods and Nature Structural & Molecular Biology present a collection that brings together reviews, classic papers, announcements and specially commissioned Comments by researchers from diverse areas of structural biology who share their views on both the past and future of the field.

Editorials and Comments

Artistic techniques are essential tools to visualize, understand and disseminate the results of scientific research. The field of structural biology has enjoyed a particularly productive marriage of art and science.

Comment | | Nature Structural & Molecular Biology

Cryo-EM has emerged rapidly as a method for determining high-resolution structures of biological macromolecules. The author of this Commentary discusses just how much better this technology may get and how fast such developments are likely to happen.

Commentary | | Nature Methods

The editors of Nature Structural & Molecular Biology have assembled a special Essay Collection, coinciding with the 40th anniversary of the Protein Data Bank, to reflect on the history and future of structural biology. These personal accounts collectively tell the history of structural biology and provide perspectives on the direction of the field and challenges that it faces.

Essay | | Nature Structural & Molecular Biology

Reviews and Perspectives

Correlated light and electron microscopy (CLEM) gives context to biomolecules studied with fluorescence microscopy. This Review discusses recent improvements and guides readers on probes, instrumentation and sample preparation to implement CLEM.

Review Article | | Nature Methods

This Perspective discusses the power of large mutational scans for the study of protein properties, the analytical challenges posed by the resulting data sets and the potential of this approach to further our understanding of human genetic variation.

Perspective | | Nature Methods

Announcements

This report describes the outcomes of the Data Management Challenges in 3D Electron Microscopy workshop. Key topics discussed include data models, validation and raw-data archiving. The meeting participants agreed that the EMDataBank should take the lead in addressing these issues, and concrete action points were agreed upon that will have a substantial impact on the accessibility of three-dimensional EM data in biology and medicine.

Commentary | Open Access | | Nature Structural & Molecular Biology

The PLUMED consortium unifies developers and contributors to PLUMED, an open-source library for enhanced-sampling, free-energy calculations and the analysis of molecular dynamics simulations. Here, we outline our efforts to promote transparency and reproducibility by disseminating protocols for enhanced-sampling molecular simulations.

Comment | | Nature Methods

Classic Papers

To understand how a protein performs its individual biological function, it is essential to know its three-dimensional structure. As early as 1934, J.D. Bernal and Dorothy Hodgkin (then Dorothy Crowfoot) showed [Bernal, J. D. & Crowfoot, D. Nature 133, 794–795 (1934)] that proteins, when crystallized, would diffract X-rays to produce a complex pattern of spots. They knew that these patterns contained all the information needed to determine a protein–s structure but, frustratingly, that information could not be deciphered. By comparing patterns from crystals containing different heavy-metal atoms, Max Perutz and colleagues devised the approach that was to solve this riddle. In 1958, J. C. Kendrew et al. applied Perutz–s technique to produce the first three-dimensional images of any protein - myoglobin, the protein used by muscles to store oxygen.

Article | | Nature

High-throughput analyses of macromolecular shape and oligomeric state at 15 Å resolution are possible with a partially automated small angle X-ray scattering (SAXS) pipeline. Though X-ray crystallography provides higher-resolution structural information than SAXS, SAXS analysis is faster and has a higher success rate, which may have implications for how structural genomics research is performed.

Article | | Nature Methods

The start-up of the Linac Coherent Light Source (LCLS), the new femtosecond hard X-ray laser facility in Stanford, California, has brought high expectations of a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. Two papers in this issue of Nature present proof-of-concept experiments showing the LCLS in action. Chapman et al. tackle structure determination from nanocrystals of macromolecules that cannot be grown in large crystals. They obtain more than three million diffraction patterns from a stream of nanocrystals of the membrane protein photosystem I, and assemble a three-dimensional data set for this protein. Seibert et al. obtain images of a non-crystalline biological sample, mimivirus, by injecting a beam of cooled mimivirus particles into the X-ray beam.

Letter | | Nature

The combination of a direct electron-detection camera that can count individual electrons and an algorithm for correcting for beam-induced motion in cryo-EM will facilitate determination of three-dimensional structures of smaller, lower-symmetry macromolecular complexes to higher resolution than previously possible.

Article | | Nature Methods