Imagine if the body had a mechanism to scan cells for flawed DNA, and another mechanism to try to repair such cells. It turns out that the body does have such mechanisms. Dr. Michael Feig heads a group of researchers who study how these mechanisms operate, as well as other questions about the structure and dynamics of proteins and nucleic acids. They use MSU’s High Performance Computing Center (HPCC) to perform simulations to facilitate their research.
Dr. Feig says that 10 years ago computers could only handle simulations involving small proteins, and could only handle simple, static models. Today, he explains, high-performance computers can simulate large biological molecules in a dynamic way, and over many time scales. His group uses computer simulation to model scales from nanoseconds to microseconds to milliseconds. That means taking analyzing events of billionths of a second, millionths of a second, and thousandths of a second . (A nanosecond is 1 millionth shorter than a millisecond.)
Experimentation in this field is mostly static – snapshots, Dr. Feig explains. “But computers can provide the movies” he says. The simulations his group does to produce the movies take 6 to 12 months using the HPCC computers. “We always think we can perform our simulations in a month or two” he says, “but in reality we need more time than we expect.” One thing is clear: these computations would take years to complete using conventional computing resources.
Dr. Feig describes how proteins in plants and animals detect flaws in DNA and initiate repairs. In bacteria or in humans, the protein MutS “scans” cells to find places where DNA fails to follow the rules of the double helix. When it finds such a cell, MutS calls on other proteins – MutL and MutH – to come to the rescue, and attempt repairs.
“Normally,” Dr. Feig says, “these repairs work.” But when attempts to repair flawed DNA fail, cancer can result. If the MutS protein itself is defective, cancer is likely. His group studies, for instance, colon cancer, where this risk is especially high. He says “Every time a cell divides, one or two out of billions will be defective. But we don’t understand fully how MutS and MutL communicate.” Better understanding of these processes could lead to better detection and treatment.
Dr. Feig’s group is in the third year of a five year project funded by the National Science Foundation. “We’re making good progress,” he says, “though it is very challenging.” The HPCC enables elaborate simulations not otherwise possible, working with terabytes of data. “We’re building a library of our movies with hundreds of terabytes (thousands of gigabytes) of data.”
Like so many other scientists who rely on MSU’s HPCC, Dr. Feig says his group’s research would not be possible without the HPCC.
Dr. Feig is assistant professor of Biochemistry and Molecular Biology. He and colleagues have published results in a number of peer-reviewed publications. He recalls when his father brought a pioneering Tandy laptop home from the United States (a Radio Shack Model 100, which he still owns). He became hooked on computers at age 15 when his high school acquired an IBM PC. Today he and his colleagues rely on computers at the HPCC with millions of times more capacity.
