Rutgers’ Protein Data Bank Powers a New Era in Structural Biology

Integrative modeling transforms how scientists understand molecular machines, with Rutgers researchers leading the global effort

The Research Collaboratory for Structural Bioinformatics Protein Data Bank, a global scientific resource based at Rutgers University-New Brunswick, has become the foundation for a new era of discovery, one that promises to reshape how scientists understand the inner workings of life itself.

At the heart of this new frontieris integrative structural biology, a powerful approach that enables scientists to learn how tiny, specialized substructures inside our cells actually work.

Brinda Vallat, associate research professor at the Institute for Quantitative Biomedicine and scientific software developer for the RCSB Protein Data Bank, is leading an effort to make a new approach accessible to scientists worldwide.

Leading the effort is Brinda Vallat, associate research professor at the Institute for Quantitative Biomedicine and scientific software developer for the RCSB Protein Data Bank. Vallat has spent the past 10 years building the data infrastructure needed to archive and deliver integrative structures to the world.

Integrative structural biology combines different types of scientific data and computer modeling to build a complete picture of large, complex macromolecules, Vallat said.

"It's a major leap forward, allowing researchers to understand not just what these molecular machines look like, but how they move, interact and function," she said.

Such knowledge, she added, could lead to new scientific breakthroughs and deeper insights into diseases.

The Protein Data Bank is a giant online library containing the 3D structures of molecules of life, such as proteins, DNA and RNA, viruses and large molecular machines. Scientists from all over the world send in their discoveries, and the Protein Data Bank researchers organize and share them for free so anyone can study how the molecules look and work.

Now, integrative structures have been made available to researchers worldwide via Rutgers' flagship website, RCSB.org.

"We are being very forward-facing to enable next-generation science," Vallat said. "These are not just static structures anymore. We can interpret their dynamics and function."

Eventually, you'll be able to model a human cell.

Helen Berman

Co-founder of the Protein Data Bank and professor emerita

Vallat is presenting a webinar, "Exploring Integrative Structures," on Nov. 12.

In the past, researchers could study structures of molecules using specialized tools such as X-ray crystallography, nuclear magnetic resonance and electron microscopy techniques. But many of the most important parts of human biology, such as the system that controls what goes in and out of a cell's nucleus, are made up of hundreds of molecules working together. This makes them too large to be deciphered by any one technique.

Stephen K. Burley, director of the RCSB Protein Data Bank, sees integrative structures as the future of biomedical research.

"They will allow us to understand biology at the level of molecular machines," he said.

One striking example, he said, is the nuclear pore complex, an assembly of more than 500 proteins that regulates molecular traffic in and out of the cell nucleus. Conventional methods could only capture fragments of this enormous structure. Integrative modeling, however, has enabled scientists to visualize the entire complex and how it assembles.

These 3D integrative structures are tools for drug discovery, disease research and biomedical innovation.

"By making these data freely available through the Protein Data Bank, Rutgers researchers are helping scientists around the world unlock the secrets of life's most intricate machinery," said Burley, who also is University Professor and Henry Rutgers Chair in the Department of Chemistry and Chemical Biology at the School of Arts and Sciences and interim director of the Rutgers Artificial Intelligence and Data Science Collaboratory. "These are the drug discovery targets of tomorrow."

Christine Zardecki, associate director of the RCSB Protein Data Bank, highlighted the collaborative nature of the work, saying the bank "is a central repository that curates, validates and shares structural data freely with the global community,"

"There are no restrictions on usage and no fees, including for access to the new integrative structures," she said. "Anyone can pull the information into their lab or company and use it for whatever purpose they want."

This image of the nuclear pore complex, a macromolecule in every human cell, focuses on some of its peripheral regions that are functionally important.

The seeds of these advances were planted more than a decade ago by Helen Berman, co-founder of the Protein Data Bank and professor emerita at Rutgers. In 2013, Berman, working with the Worldwide Protein Data Bank consortium and Andrej Sali of the University of California, San Francisco, co-organized a workshop in the UK to address the rising need to archive structures derived from multiple methods.

"We brought together people doing all different kinds of biophysical and computational methods," Berman said. "We decided we needed a systematic approach to working on these kinds of structures."

That workshop led to a white paper, a grant and the hiring of Vallat to build the system that now powers integrative structure archiving.

"Eventually you'll be able to model a human cell," Berman said. "If we just keep working like this, we'll be able to understand interactions within the cell and things like that."

Recognizing the global importance of PDB data, the Rutgers group co-founded the Worldwide Protein Data Bankconsortium with partners in Europe and Asia. Today, the Worldwide Protein Data Bank jointly manages the PDB and related specialist archives.

The RCSB Protein Data Bank is supported by grants from the U.S. National Science Foundation, the U.S. Department of Energy, the National Cancer Institute, the National Institute of Allergy and Infectious Diseasesand the National Institute of General Medical Sciencesof the National Institutes of Health.

The Protein Data Bank, used by many millions of researchers and students around the world, "was the best kept secret at Rutgers for forever," Burley said. "Now it's time to tell the world."

Explore more of the ways Rutgers research is shaping the future.