Studying HIV at the Molecular Level
Michigan State University chemistry Professor Robert Cukier uses a technique known as molecular dynamics to look at the human immunodeficiency virus (HIV) at an atom-by-atom level.
Working with a team of collaborators, Cukier is exploring how HIV behaves, for instance, when interacting with a drug: how potential drugs “dock” with the virus or why a strain of HIV that has become multi-drug-resistant (MDR) is different from others.
The researchers begin with an X-ray crystallography image. “The image is like a snapshot of the virus,” says Cukier. “You can’t capture moving images using crystallography; it’s like having a single frame from a movie,” he explains. Starting with the snapshot, he uses computer simulations to model how the molecule will behave when heated in order to determine how protease “flaps” on the virus behave.
The study hones in on a “femtosecond” of time – 1 to the 10 to the minus 15th of a second. The researchers also analyze behavior in terms of picoseconds (1 to the 10 to the minus 12th); nanoseconds (a billionth of a second), microseconds (millionths of a second) all the way to one second. The goal is to try to find at what interval the fastest motion occurs.
Modeling over such a wide range of intervals produces a massive amount of data and requires an immense amount of computational power. Cukier says “We’ve solving Newton’s equations and these are very expensive calculations. In theory, we’re solving a problem 10 to the 15 times.”
One modeling run used 8 processors on an SGI computer in the High Performance Computer Center (HPCC) at MSU. The program emitted intermediate results every 250 steps, so research could recover in event of a computer outage. Cukier estimates that they produced a terabyte (a thousand gigabytes) of results. The analysis took three months to complete.