The Nobel And Beyond
David Baker earns Nobel Prize for protein design with supercomputing behind the discovery
The Royal Swedish Academy of Sciences awarded half of the 2024 Nobel Prize in chemistry to David Baker of the University of Washington “for computational protein design” in pioneering work that has been long supported by TACC.
Baker uses supercomputers to predict how proteins fold. Their shape reveals important reactive properties such as electrostatic potential and hydrophobicity, knowledge that can lead to developing new medicines.
Starting in the early 2000s, Baker’s lab used the National Science Foundation (NSF)-supported Protein Data Bank library for its first protein structure design algorithms and later protein design tools for which Baker’s portion of the Nobel Prize was awarded. This work led to the development of the Rosetta software for “ab initio” (from scratch) structure prediction of small proteins.
In 2020, the Baker Lab was awarded allocations on TACC’s Stampede2 supercomputer to calculate the shapes of millions of proteins using Rosetta for further testing in the lab and to computationally test how well the designed proteins can dock to targets such as the COVID-19 spike protein. “Centers like TACC play a critical role in urgent computing efforts as much as they do in scientific research generally,” Baker said.
In May 2023, Baker and colleagues at the Institute for Protein Design, which he heads, published work in Nature Communications that acknowledged support by TACC’s NSF-funded Frontera, the most powerful academic supercomputer in the United States. Baker’s allocation used 382,000 node hours for his protein design research. The team used Frontera for deep learning, a method that augmented existing physical models in “de novo” (from the beginning) computational protein design, resulting in a tenfold increase in success rates for binding a designed protein with its target protein.
“Protein design holds transformative potential to address societal challenges by enabling the discovery of once unimaginable structures,” said former NSF Director Sethuraman Panchanathan. “Decades of federal investments in fundamental research and infrastructure, combined with industry innovation, have yielded tools that significantly impact everyday life.”
TACC is making an important contribution toward the creation of a whole new world of designed proteins to address current challenges.
“TACC is making an important contribution toward the creation of a whole new world of designed proteins to address current challenges,” Baker concluded.
His pioneering research is pushing the boundaries of biological modeling, leveraging TACC’s Lonestar6 supercomputer to drive groundbreaking biochemical discoveries. By designing human-like antibodies — proteins that precisely target disease and activate immune defenses — his work is advancing powerful new treatments for cancer, autoimmune disorders, and infectious diseases.