How You, and Your Computer, Can Play Scientist

Two heads are better than one. The ethos behind the scientific research project Folding@home is that same idea, multiplied: 50,000 computers are better than one.

Folding@home is a distributed computing project which is used to simulate protein folding, or how protein molecules assemble themselves into 3-D shapes. Research into protein folding allows scientists to better understand how these molecules function or malfunction inside the human body. Often, mutations in proteins influence the progression of many diseases like Alzheimer’s disease, cancer, and even COVID-19.

Penn is home to both the computer brains and human minds behind the Folding@home project which, with its network, forms the largest supercomputer in the world. All of that computing power continually works together to answer scientific questions such as what areas of specific protein implicated in Parkinson’s disease may be susceptible to medication or other treatment.

Science Powered by Your Home Computer

A close-up image of a supercomputer with green glowing lights

Led by Gregory Bowman, PhD, a Penn Integrates Knowledge endowed professor of Biochemistry and Biophysics in the Perelman School of Medicine at the University of Pennsylvania, Folding@home is open for any individual around the world to participate in and essentially volunteer their computer to join a huge network of computers and do research.

Using the network hub at Penn, Bowman and his team assign experiments to each individual computer which communicates with other computers and feeds info back to Philly. To date, the network is comprised of more than 50,000 computers spread across the world.   

“What we do is like drawing a map,” said Bowman, explaining how the networked computers work together in a type of system that experts call Markov state models. “Each computer is like a driver visiting different places and reporting back info on those locations so we can get a sense of the landscape.”

Individuals can participate by signing up and then installing software to their standard personal desktop or laptop. Participants can direct the software to run in the background and limit it to a certain percentage of processing power or have the software run only when the computer is idle.

When the software is at work, it’s conducting unique experiments designed and assigned by Bowman and his team back at Penn. Users can play scientist and watch the results of simulations and monitor the data in real time, or they can simply let their computer do the work while they go about their lives.

Bowman added that the team is careful about the safety of the individual computers that connect to the project by employing cryptographic methods like digital signatures to keep a data firewall. “We ensure that the software will only run code that we provide and not things sent by malignant actors,” he said. “We also only allow a set of functions related to molecular dynamics simulations to run.”

Those who volunteer to participate can know that they’re exponentially increasing the speed at which experiments can be conducted. One recent experiment that Bowman is working on (related to antibiotic resistance) would take a top-of-the-line MacBook Pro roughly 500 years to complete on its own. It takes his computer just two weeks to offer data.

Why Study Proteins

To understand the importance of protein research, you first have to understand the importance of proteins.

“Proteins are like little machines and are essential in just about any chemical or physical action that exists,” said Bowman. “They are behind our bodies’ natural processes, and if something goes wrong, proteins are likely to blame.”

To build the proteins needed in the body, cells have a construction process that involves connecting component molecules, amino acids, in a specific linear order unique to each type of protein, like beads on a string. But a line is not the proteins’ natural shape. Prior to taking any sort of action, most proteins fold. Usually, they fold in expected and “normal” ways. Folded proteins also have many moving parts that are essential to their ability to function. When the shape or motion of a folding (or an already folded) protein goes awry, the biological and chemical mechanisms functions of that protein might not work correctly. 

Folding@home helps to build maps and offer a virtual “view” of the world of proteins that are too small to actually see. There are no microscopes powerful enough to give us a picture of these protein dynamics in how the molecules fold into complex shapes and shift into different shapes. Scientists rely on calculations and computations to visualize these shapes, which underscores the value of the world’s largest super computer and its ability to simulate protein processes.

One of the aspects of protein structure that Bowman and his colleagues are investigating through simulations is cryptic pockets. These are hidden areas of the protein structure easy for other molecules, including new or existing drug treatments, to bind to. Bowman and his team recently used Folding@home to identify potential cryptic pockets in cancer-related protein structures and saw that likely 50 percent of these structures once considered “undruggable” may in fact be vulnerable to drugs.  

The Future of Folding@home

Bowman’s mentor and PhD advisor at Stanford University, Vijay Pande, PhD, who now works as a venture capitalist, first fired up this computer project back in 2000. After developing the proper code, the first experiments were simulations of the folding of peptides, tiny parts of proteins. Bowman began working on Folding@home when he was a PhD candidate in 2006. His work focused on writing formulas to create the maps, or the Markov state models, that have been a foundation of the work since. Bowman became director of the program in 2018 while at Washington University in St. Louis and moved to Penn last summer, bringing Folding@home with him.

One of the many characteristics Bowman found appealing about Penn was the leading research taking place with cancer, specifically the Basser Center for BRCA in the Abramson Cancer Center and Penn’s efforts in BRCA research. Bowman hopes to uncover how to drug proteins related to the BRCA1 and BRCA2 genes which, when mutated, can lead to breast, ovarian, prostate, and pancreatic cancers.

Like many researchers, Bowman is driven by scientific exploration and the future possibilities of medical advancement. As an individual with a visual impairment, he became motivated in middle school to understand basic science and the biological mechanisms underlying his disease and others.

“At the time, sequencing the human middle and the cloning of Dolly the sheep were big news, and I was inspired to pursue a career in biomedical research with the aim of helping to lay the foundation for advances that would someday cure diseases like mine,” he said.

While labs were often not accessible places for those with visual impairments, Bowman developed a love of computers and realized computer research was a way he could play a significant part in biomedical research.   Now, as an established and accomplished scientist, Bowman’s plan for Folding@home is one of continuation and growth.

“I’m really excited about our ability to do large-scale comparative studies,” he said. “Instead of studying one protein, we can now study a dozen related proteins in parallel and then compare and contrast the results to learn what gives rise to the unique and common properties of each protein. We can also compare the interactions between a protein and tens of thousands of different chemical compounds to learn which might be the most valuable starting points for drug design.”

Those looking to be part of the research and put their computer to work can visit Foldingathome.org to install the program and join the network.

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