Science 101: Structural Biology

What Is Structural Biology?

Proteins are essential for almost everything our bodies do. They help us see, fight infections, repair cells and even control how we use energy. Structural biology is the study of 3D shapes of proteins to understand their function or how they work. This is important because many diseases happen when proteins don’t work properly — they might be too active, not active enough, improperly shaped (folded), or malfunctioning in some other way.

Proteins are made from chains of smaller building blocks called amino acids. These chains are built using instructions from DNA. After they’re made, the chains fold into specific 3D shapes. A protein’s shape determines its job, like carrying oxygen, sending signals, or speeding up chemical reactions. Structural biology focuses on figuring out how a protein’s shape is connected to its function.

To study proteins, scientists first make large amounts of a specific protein in the lab. They purify the protein and then try to grow crystals from it. Protein crystals are made up of millions of identical protein molecules arranged in an orderly pattern. These crystals help scientists study proteins in great detail.

One of the most powerful ways to study protein crystals is by using X-ray diffraction. Scientists shine X-rays through the crystal, and the atoms inside scatter the rays, creating a unique pattern. By analyzing this pattern with advanced computational methods, scientists can determine the positions of individual atoms and reconstruct the protein’s 3D structure. This process is like solving a puzzle to see how the protein is folded.

Growing protein crystals is tricky. Scientists place proteins in trays with special chemicals that help them form crystals. Once the crystals grow to about the width of a human hair, they are carefully collected under a microscope. To protect the crystals, they are quickly cooled in liquid nitrogen and sent to advanced facilities like the Advanced Photon Source (APS) for data collection.

Even though scientists know the order of amino acids in a protein, they cannot reliably predict its final folded shape from sequence alone. It’s like knowing the order of beads on a necklace but not knowing how the necklace will hang when worn. X-ray diffraction is essential for determining the protein’s shape.

Artificial intelligence (AI) is also helping scientists predict protein shapes. AI tools learn from hundreds of thousands of known protein structures stored in the Protein Data Bank. While AI predictions are useful, they aren’t always detailed enough for things like drug development, so scientists still need to confirm the shapes experimentally.

New technology is improving structural biology. Advanced X-ray facilities like the APS can focus highly intense beams onto crystals as small as one micron — about one-hundredth the width of a human hair. In a technique called serial crystallography, data is collected from tens to hundreds of thousands of micron-sized crystals to create a complete, high-resolution data set with minimal radiation damage. These powerful X-rays enable scientists to gather data quickly and determine many protein structures within a single day.

Once scientists figure out a protein’s structure, they add it to the Protein Data Bank. These data become freely available to researchers worldwide. This information helps with drug discovery and the design of treatments. By revealing how proteins function at the atomic level, structural biology provides a foundation for understanding biology, guides drug discovery and improves human health.