A Protein Folding Mystery Solved: Study Explains Core Packing Fractions
17th April 2025
In living organisms, every protein—a type of biological polymer consisting of hundreds of amino acids—carries out specific functions, such as catalysis, molecule transport, or DNA repair. To perform these functions, they must fold up into specific shapes. It’s a complex process that’s critical to life, and despite advances in the field, there remain many open questions about the process.
Proteins are the toolbox of cellular life. The whole purpose of DNA and RNA is to create the proper proteins.
The researchers, led by Corey O’Hern, developed computational models for all globular proteins in the Protein Data Bank, an online database, and measured their interior core regions to determine how densely packed they were. Every protein had a core packing fraction of 55%. That is, 55% of the space was occupied by atoms. That led the research team to two questions.
“Why did they all have the same value? And, specifically, why is the value 55%?” said O’Hern, professor of mechanical engineering, materials science, physics, and applied physics. “The answer seems to be that the packing fraction stops increasing when the protein cores jam or rigidify.”
That is, the individual amino acids that make up the protein core couldn’t compress any further when the protein folded. The packing fraction at which objects jam together depends largely on their shape. Spherical objects, for instance, jam at a packing fraction of 64%.