A new chapter for RCSB Protein Data Bank Molecule of the Month in 2025

The Protein Data Bank (PDB) is the singular global resource archiving public-domain 3D atomic coordinates of biological molecules.¹ It currently provides access to >230 000 structures and supports a broad community of users numbering in the many millions, including the structural biologists who determine these structures, scientists who use these structures to provide atomic-level insight in their research, and educators looking for exciting examples of biomolecular structure/function to incorporate into their lessons.

Research Collaboratory for Structural Biology (RCSB) Protein Data Bank (PDB) is one of the Worldwide Protein Data Bank (wwPDB) partner organizations responsible for managing the deposition, validation, and biocuration of 3D biostructure information.^2,3 As the wwPDB-designated Archive Keeper, RCSB PDB is responsible for safeguarding the archival contents, which today has a replacement value of greater than US$23 billion. RCSB PDB and its wwPDB partners freely distribute identical PDB data to anyone working or learning anywhere in the world with no limitations on its usage. RCSB PDB develops resources to search, visualize, and analyze PDB structures and more than one million computed structure models (CSMs) at RCSB.org.^4,5 The RCSB PDB organization is committed to telling the stories of the PDB archive and created PDB-101 in 2011 to provide a one-stop web portal for training, education, and outreach materials (PDB101.RCSB.org⁶).

Molecule of the Month is the flagship feature of PDB-101. With more than 300 published articles, the series continues to provide user-friendly entry points into the PDB archive and RCSB.org resources.^7–9 It is an exemplar of “Education, Outreach, and Research Applications” used by the structural science community as highlighted at the 2024 Transactions Symposium of the American Crystallographic Association.¹⁰ Each installment focuses on the structure and function of an interesting biological macromolecule, discusses the relevance of the molecule to human health and welfare, and perhaps most importantly, suggests how PDB101.RCSB.org visitors may view these structures and access additional details. The Molecule of the Month archive is accompanied by a diverse collection of PDB-101 multi-modal training and outreach materials, including illustrations, videos, interactive animations, coloring activities, games, and curricula.

Every installment of the Molecule of the Month builds on strong traditions of scientific communication to improve the comprehensibility of the molecular stories. Three core principles underpin our storytelling process: reducing technical jargon in the text and illustrations, presenting structures as part of a contextual story, and showing dynamic and biochemical processes.¹⁰ Creating accessible and attractive illustrations is a critical part of our process. We carefully consider views and rendering styles that clearly convey the overall shape and function of the molecule. The illustrations must also be engaging and easily readable to broad audiences. Open access to these illustrations also encourages sharing and reuse by others.

Over the past 25 years, topics covered in the Molecule of the Month have ranged across the subdisciplines of biomolecular science and technology, covering many of the basic principles of biomolecular structure and function. Selected examples are presented in Fig. 1. Topics are chosen with a variety of goals in mind. Many articles highlight exciting new 3D biostructures determined with financial support from the National Institutes of Health, the US National Science Foundation, and the US Department of Energy. These same funding agencies support RCSB PDB core operations. Other topics are those commonly discussed in classrooms (e.g., DNA and hemoglobin). Emerging technologies (e.g., cryo-electron microscopy, X-ray Free Electron Laser (XFEL)) and high-profile current events (e.g., plastic-eating enzymes, influenza A H5/N1 virus) have also been explored. Additionally, subjects are selected to support other PDB-101 initiatives, including a biannual Focus theme (e.g., Peak Performance, 2024–2025).

To make these diverse features findable and accessible, users may search PDB-101 holdings by text and view articles by date or title or browsing manually curated categories. These categories and the number of articles represented therein are enumerated in Table I. The main category browser also links to many related PDB-101 resources (e.g., videos, paper models, and posters).

As the science of structural biology has expanded, PDB-101 has grown in parallel. Two major developments have changed the way structural biology is done, posing new challenges for both the PDB archive and introductory materials supporting its users: cryo-electron microscopy¹¹ and the availability of computed structure models of protein structures generated with artificial intelligence (AI)/machine learning (ML) methods, more than a million of which have been integrated with the RCSB.org website.^3,5,12

Cryo-electron microscopy is being used to determine structures of unprecedented size and complexity, posing new challenges for storytelling.¹¹ These structures are typically large assemblies consisting of multiple proteins and/or nucleic acid chains, so a hierarchical approach must be taken to explore and present their function. A multi-resolution approach has proven effective, using reduced representations to explore the assembly of subunits into the entire complex and smoothly moving to atomic representations when presenting details of active sites or molecular interfaces.

Computed structure models (CSMs) pose orthogonal challenges. With current methods, such as AlphaFold2^13,14 and RoseTTAFold,¹⁵ these structural models typically include only a single protein chain with no bound cofactors or ligands. Accuracy of these CSMs ranges from high to very low, which poses multiple challenges for storytelling. Careful explanation is required as to which aspects of the CSM may be trusted, and how they are relevant to the structure/function of the story being told. The great advantage, of course, is that CSMs may be predicted from any protein sequence, allowing, for example, 3D comparisons of proteins with similar biological/biochemical function from distinct organisms or exploration of biomolecules that have not been amenable to experimental structure determination.

The Molecule of the Month will continue to grow to support the new possibilities provided by these and other cutting-edge technologies. In particular, molecular animation is a powerful tool for guiding users through the complexities of large biomolecular assemblies and their dynamics in an intuitive way. In Janet Iwasa's maiden article published in January 2025,¹⁶ animation was used to exemplify the dynamics of “assembly line-like” polyketide synthases (Fig. 2). Describing molecular movements using animation poses its challenges, however. Most notably, experimental data depicting a dynamic molecular process are often incomplete and require some amount of extrapolation or conjecture to tell a complete story. To mitigate this issue, textual explanations, annotations, and visual cues may be used to indicate uncertainty.

The PDB archive has been committed to open access since it was established in 1971.¹⁹ That commitment is continued throughout PDB-101, which makes all training, outreach, and educational materials free for use and reuse. Open access has been important to enabling the widest possible usage of PDB-101 materials. The success of this approach is exemplified by usage statistics of the Molecule of the Month. In 2024, the collection of Molecule of the Month articles was accessed ∼690 000 times by users around the world (Google Analytics). The installment exploring hemoglobin, presented over 20 years ago, is still the most highly accessed topic (∼19 K views in 2024), and, indeed, multiple articles such as collagen (∼13 K views in 2024) and insulin (∼13 K views in 2024) have shown similar wide and consistent usage.⁷ Molecule of the Month articles on emerging topics are also widely shared and reused. For example, content related to COVID-19 has hosted heavy traffic and was widely shared in news articles and social media.²⁰ 

Molecule of the Month illustrations are available under a CC-BY-4.0 license and are made available as high-resolution image files to encourage all types of reuse. Anecdotal examples of Molecule of the Month content include images in presentations and teaching activities built around the topics, for example, challenging students to choose a molecule and dig deeper or posing a classroom-wide scavenger hunt. Illustrations have been reproduced in the public sphere through public newspapers, magazine covers, and externally produced training materials, and in private use in the form of socks, hats, home decoration, and more.

The Molecule of the Month also served as a training ground for graduate and undergraduate students in week-long “Boot Camps” on Science Communication in Biology and Medicine hosted by the Institute for Quantitative Biomedicine at Rutgers University. In this one-week event, students were trained in scientific communication and then collaborated to author installments of the Molecule of the Month on Fundamental Biology^21–26 and Cancer.^27–36 

David Goodsell led creation of the series for the first 300 articles. In January 2025, he passed the baton to Janet Iwasa. Future installments will continue to highlight the important stories of the PDB archive to enable training, outreach, and education efforts worldwide.

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the U.S. Department of Energy (DE-SC0019749), and the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of General Medical Sciences of the National Institutes of Health under Grant No. R01GM157729. The Molecule of the Month benefits from collaborations and contributions from many people, and the authors thank past coauthors, expert reviewers, and software developers. From the RCSB PDB, we are grateful for the efforts of Charmi Bhikadiya, Cole Christie, Luigi DiConstanzo, Shuchismita Dutta, Rachel Kramer Green, Rob Lowe, Dennis W. Piehl, and Maria Voigt for helping make the series possible and accessible.

The authors have no conflicts to disclose.

Janet Iwasa: Conceptualization (equal); Visualization (equal); Writing – original draft (equal); Writing – review & editing (equal). David S. Goodsell: Conceptualization (equal); Visualization (equal); Writing – original draft (equal); Writing – review & editing (equal). Stephen K. Burley: Conceptualization (supporting); Funding acquisition (lead); Supervision (supporting); Writing – review & editing (equal). Christine Zardecki: Conceptualization (supporting); Project administration (lead); Writing – original draft (equal); Writing – review & editing (equal).

Data sharing is not applicable to this article as no new data were created or analyzed in this study.