The research, now published in 'PRX Life', highlights the role AI can play in advancing scientific discovery by decades. "This work gives us a better idea of how you might design a new protein to withstand stress and new clues into what types of proteins would be more likely to exist in high-pressure environments like those at the bottom of the ocean or on a different planet," said Stephen Fried, a chemist from Johns Hopkins University who co-led the study.
Fried's team studied 'Thermus thermophilus', a microorganism known for its heat resistance, under pressures mimicking those in the Mariana Trench. The findings revealed that some proteins in the microbe resist pressure by having extra space within their atomic structure, which allows them to compress without collapsing.
A protein's function is determined by how its amino acid chains fold into 3D structures, but these folds are often sensitive to environmental factors like pressure. Fried's team found that 60% of the proteins resisted pressure, while others deformed, often at biochemically important sites. This understanding could shed light on how organisms adapt to extreme environments.
"Life has obviously had an evolutionary drive to adapt to different environments over billions of years, but evolution can sometimes almost sound like a magical thing," said Fried. "Here, we really get down to the biophysics of how that happens and see it's because of a simple geometrical solution in the 3D arrangement of these proteins' building blocks."
The team used Google's AlphaFold tool to map over 2,500 proteins in 'T. thermophilus'. AI helped predict the proteins' structures, revealing how they resist pressure changes - a process that would have taken decades through direct measurement, Fried explained.
Although 'T. thermophilus' is better known for thriving in hot environments rather than deep-sea pressures, the findings offer a better understanding of how organisms survive in extreme environments, including the deep ocean, which remains vastly understudied. "A lot of people predict if we are going to find extraterrestrial life, we're going to find it deep in the ocean of some planet or moon," said Johns Hopkins chemist Haley Moran. "But we don't fully understand life in our own ocean, where there are many different species that don't just tolerate what would kill us, they love it and thrive in it."
The research suggests that high-pressure experiments could reveal previously hidden molecular functions in other organisms. "We were really caught by surprise," said Richard Gillilan of Cornell University, who helped develop the high-pressure tests. "We realized this was a treasure map. We have opened a door that will provide many new targets for structural and biophysical studies, perhaps even drug discovery."
The team now plans to study other organisms thriving in high-pressure environments in the deep ocean.
Other authors include Edgar Manriquez-Sandoval and Piyoosh Sharma of Johns Hopkins.
Research Report:Proteome-Wide Assessment of Protein Structural Perturbations under High Pressure
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