PDB 50th Anniversary: celebrating the future of structural biology

The Protein Data Bank (PDB) is the primary data resource for structural biology. On its 50th anniversary, we celebrate the future of this ever-growing field.

We celebrate the 50th anniversary of the Protein Data Bank together with our colleagues at Nature Methods with a special collection that showcases key achievements in structural biology and views of its future.

The Protein Data Bank (PDB) is a community resource. But how do we define community, and how has it changed over the last 50 years since the PDB was founded? How did the community influence the evolution of the PDB, and how did the PDB influence both the science and the behavior of the community?

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.

Biocurators, the backbone of the wwPDB, manage structural biology data deposition, quality, and integrity, and provide integral support to the research community worldwide.

The future of macromolecular crystallography includes new X-ray sources, enhanced remote-accessible capabilities and time-resolved methods to capture intermediate structures along reaction pathways.

It is time for structural biologists to embrace the challenge of quantitatively describing functional energy landscapes.

Many challenges and considerations must be evaluated when expanding and supporting new cryo-electron microscopy facilities.

Advances in cryo-EM technology will open a new era of RNA-only 3D structure determination.

Interest in cryo-ET is rapidly growing, but many technical challenges still require solutions.

Cryo-ET, which yields both structural and spatial information, will help unlock the molecular architecture of cells.

Computational protein modeling rapidly advances structural knowledge of viral proteins, but methods for modeling protein complexes still need improvement.

Whole-cell models, still in the early stages of development, are poised to open the next frontier in integrative modeling.

Integrative structural biology, the culmination of experimental and theoretical methods, will provide a holistic view of molecular processes.

Single-particle techniques offer an unprecedented opportunity to understand the role of structural variability in biological function. They also call into question the meaning of ‘a structure’ and its relevance to function.

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.

Single-particle cryo-electron microscopy (cryo-EM) has emerged over the last two decades as a technique capable of studying the structure of challenging systems. The author of this Commentary discusses some of the major historical landmarks in cryo-EM that have led to its present success.

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.

The quality of structural data obtained in cryo-EM is affected by multiple factors pertaining to sample preparation. This Review discusses available techniques and current challenges.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

This paper reviews the cryo-EM technique of microcrystal electron diffraction (MicroED), providing a broad overview of the technique, the unique structures determined, and the opportunities for future development.

Members of the hydrogen deuterium exchange mass spectrometry (HDX-MS) community provide their ‘best practices’ recommendations for HDX-MS data collection, analysis and reporting.

An interactive online resource integrated in the GPCRdb hub presents tools to design GPCR constructs and determine appropriate experimental conditions for structural studies by crystallography and cryo-EM.

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.

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.

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.

The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.

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.

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.

The start-up of the new femtosecond hard X-ray laser facility in Stanford, the Linac Coherent Light Source, has brought high expectations for a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. This new capability is tested for the problem of structure determination from nanocrystals of macromolecules that cannot be grown in large crystals. Over three million diffraction patterns were collected from a stream of nanocrystals of the membrane protein complex photosystem I, which allowed the assembly of a three-dimensional data set for this protein, and proves the concept of this imaging technique.

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.

AlphaFold predicts the distances between pairs of residues, is used to construct potentials of mean force that accurately describe the shape of a protein and can be optimized with gradient descent to predict protein structures.