How do scientists use protein structures to develop new drugs?
Drugs typically work by either blocking or supporting the activity of specific proteins in the body. Using an approach called structure-based drug design, scientists can make a template for a protein and use that blueprint for creating new medicines. They start with a computerized model of the protein structure they’re interested in studying. For example, the computer model would allow researchers to examine how two proteins work together. Then, if scientists want to turn off one protein, they would try to design a molecule that would block or alter that interaction.
What’s an example of a medicine developed using structure-based drug design?
Researchers used structure-based drug design to develop some anti-HIV drugs. HIV protease is an enzyme that keeps the virus alive. Knowing its structure allowed researchers to determine the kinds of molecules that could stop HIV protease from working. Scientists used computer models to fine tune molecules that could halt virus production. This work led to medicines called protease inhibitors.
How do scientists determine protein structures?
Researchers use several imaging techniques to determine the structure of proteins and other complex molecules. Cryo-electron microscopy (cryo-EM) allows scientists to “see” individual proteins as well as larger structures such as molecular complexes (groups of proteins that combine and function as a unit), viruses, or organelles (specialized structures within the cell that perform specific functions). X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy also make it possible for researchers to view proteins. To date, researchers have used these techniques to unravel the structure of more than 122,000 proteins. The Protein Data Bank stores these structures and gives scientists access to them at
What is cryo-EM, and how does it work?
In cryo-EM, researchers rapidly freeze a cell, virus, molecular complex, or other structure so that water molecules do not have time to form crystals. This preserves the sample in its natural state. Scientists use an electron microscope to blast the frozen sample with an electron beam. This creates a two-dimensional projection of the sample on a digital detector. By creating hundreds of projections of the sample from many different angles and then taking the average of these angles, scientists generate a three-dimensional model of its structure. Recent advances in cryo-EM provide highly detailed images of proteins and other biological structures, including larger structures such as RNA-protein complexes.