Breakthrough will speed development of drugs to combat viruses

Researchers in Illinois have created what is believed to be the first atomic-level computer-based simulation of a complete functioning organism.

According to the scientists, the breakthrough has the potential to speed development of new drugs to combat viruses in plants, animals and, ultimately, people.

A research team led by Professor Klaus Schulten at the University of Illinois at Urbana-Champaign simulated a plant virus with as many as one million moving atoms.

The achievement is described by the team as historic due to the sheer complexity of the problem. Had the researchers relied on today's desktop computer systems, they would not have finished until 2041.

Professor Schulten's team used part of an SGI Altix 3700 Bx2 system located at the National Center for Supercomputing Applications. The Altix system allowed them to calculate how all the atoms interact every femtosecond, or one-millionth-of-a-billionth of a second.

Although the virus is so small that biologists refer to it as a particle, the ability to simulate the organism as it functions holds tremendous promise for medical research.

"It allows us to see how the virus assembles and disassembles," said Peter Freddolino, a member of the Illinois research team which also includes physicist Anton Arkhipov.

"Because assembly and disassembly are two of the key steps in the viral life cycle, understanding these events could lead to the development of drugs designed to attack them at these vulnerable points."

The project, reported in the March issue of the scientific journal Structure, is the first successful case of biological reverse-engineering of a complete virus. "This is on the highest end of what is feasible today," said Professor Schulten.

"The approach is something that we learned from engineers: reverse engineer the subjects you're interested in and test fly them in the computer to see if they work in silico (or simulated on a computer) the way they do in vivo (in the body).

"Naturally, deeper understanding of the mechanistic properties of other more complicated viruses will eventually contribute to public health and medicine."

The smallest natural organisms known, viruses contain intricate mechanisms for infecting host cells. The Illinois researchers simulated one of the tiniest and most primitive viruses in an attempt to recreate the process of infection and propagation.

The satellite tobacco mosaic virus attacks tomato plants throughout the US, and relies on a host cell and a host virus to reproduce.

While they simulated the activity of the viral organism over just 50 nanoseconds of time, the researchers were able to determine that the virus, which appears symmetrical, actually pulses in and out in an asymmetrical pattern.

"We observed that each part of the viral structure moves a little bit on its own," noted Arkhipov, who has worked with Freddolino and Professor Schulten since the project's inception a little more than a year ago.

The team's simulated findings support observations made by others in traditional laboratory work. Those earlier observations, however, left researchers wondering what caused the behaviour - something that remained a mystery until today.