Looking beyond the sequence: New Purdue tool reveals hidden patterns in protein evolution

07-07-2026

Proteins are the tiny machines that power life, carrying out nearly every task inside living cells. While scientists have long studied the genetic code that builds these proteins, a team at Purdue University has developed a new way to see something that traditional approaches often miss: how evolution shapes proteins in three dimensions. 

The new software package, called evo3D, gives researchers a clearer picture of how proteins evolve by combining genetic information with their three-dimensional structures. The approach could help scientists better understand how viruses change over time and support future efforts to identify promising targets for vaccines and other medical advances.

The research, led by Purdue graduate student Brad Broyles and Qixin He, assistant professor of biological sciences, was published in Molecular Biology and Evolution.

"Proteins fold into complex three-dimensional shapes, and that shape determines how they function," Broyles said. "Evolution acts on those shapes, but most evolutionary studies still examine proteins as if they were just a straight line of letters."

Traditional methods compare proteins by reading their amino acid sequences from beginning to end. While those approaches have been valuable for decades, they overlook an important reality: parts of a protein that are far apart in the sequence may end up side by side once the protein folds into its final shape.

"Selection signals are hiding in 3D," He said. "By looking at proteins the way they actually exist, we can detect important evolutionary patterns that are invisible with traditional methods."

To bridge that gap, the researchers created evo3D, an open-source software package that connects genetic sequence data with protein structures. Rather than studying proteins one letter at a time, the program analyzes groups of neighboring amino acids based on where they sit in three-dimensional space.

The team demonstrated the approach using viral proteins, where it successfully identified conserved surface regions that conventional sequence-based analyses failed to detect. Those stable regions are especially important because they may serve as better targets for vaccines, which often work best when they recognize parts of a virus that change very little over time.

"Our goal was to build a bridge between sequence data and protein structure," Broyles said. "There are many questions researchers can ask once they can analyze evolution in a three-dimensional context."

The software was originally developed to support Broyles' broader research on the human immune system. Antibodies recognize three-dimensional features on the surfaces of proteins, making it important to understand how those regions evolve.

"In vaccine design, scientists often look at which individual amino acids are conserved," Broyles said. "But antibodies actually recognize groups of amino acids that form a surface patch. Looking at those patches instead of isolated positions provides a much more complete picture."

Beyond vaccine research, evo3D can be applied to many areas of biology where protein structure plays a role, including studies of infectious diseases, protein interactions and molecular evolution. The researchers designed the software to be accessible to scientists with a wide range of computational experience, lowering barriers for researchers interested in incorporating structural information into their work.

As advances in artificial intelligence make accurate protein structure prediction more widely available, Broyles believes tools like evo3D will become increasingly valuable.

"There's still a tremendous amount to discover," he said. "We hope evo3D helps researchers uncover evolutionary patterns that have been there all along—we just haven't had the right perspective to see them."

The research was supported by the National Institutes of Health, a Purdue Biological Sciences BIO-SPARK award and the Yeunkyung Woo Achieve Excellence Travel Award.

 

About the Department of Biological Sciences at Purdue University

The Department of Biological Sciences is the largest life sciences department at Purdue University. As part of Purdue One Health, we are dedicated to pioneering scientific discoveries and transformative education at the cutting edge of innovation. From molecules to cells, from tissues to organisms, from populations to ecosystems- we bring together multiple perspectives, integrating across biological scales to advance our understanding of life and tackle the world’s most pressing challenges. Learn more at bio.purdue.edu.

 

Written by: Alisha Willett, Communications Specialist, amwillet@purdue.edu

Contributors: Brad Broyles, bbroyle@purdue.edu

                        Qixin He, heqixin@purdue.edu