Computational Science Breakthrough Simulates an Entire Life Form

Researchers at the Beckman Institute for Advanced Science and Technology at the University of Illinois have made an exciting breakthrough in computational science that for the first time simulates an entire life form.

Beckman Institute researchers make history by simulating the tiny satellite tobacco mosaic virus

In a paper that will be published in the March 14, 2006 issue of the scientific journal, Structure, Klaus Schulten, Peter L. Freddolino, Anton S. Arkhipov, Steven B. Larson, and Alexander McPherson describe how they have successfully simulated the complete satellite tobacco mosaic virus.

The complete system simulated by the TCB Group at Beckman and NCSA, including the Satellite tobacco mosaic virus (protein capsid and RNA), ions, and water. The system contains a total of over one million atoms.

Klaus Schulten, director of the Theoretical and Computational Biophysics Group at the Beckman Institute, said this is a monumental step for biologists in their quest to study life.

"When Boeing or Airbus developed their latest airplanes, their engineers designed them in a computer and did test flights with computer-generated prototypes," Schulten said. "Biologists would like to do the same by reverse engineering life forms and 'test fly' them in the computer to see if they work the same in silico as in vivo."

Schulten said biologists have accomplished this already with small pieces of living cells such as the cell's proteins, but simulating an entire life form such as the satellite tobacco mosaic virus is completely novel.

Viruses, which are the causes of many diseases, are the smallest natural organisms known. Their small size and relative simplicity are what made them an excellent choice for the first attempt to use a computer program to reverse engineer a life form or living particle. Viruses are extremely primitive and parasitic and biologists often refer to them as "particles" rather than organisms. However, viruses do contain in a protein shell, the capsid, which protects the genome, which is made up of DNA or RNA. Viruses hijack a biological cell and make it produce from one virus many new ones. In order to do this, viruses have evolved elaborate mechanisms of self-assembly, entry and disassembly to infect host cells. They pack their components into their capsid and leave the host cell when it bursts from viral overcrowding.

The satellite tobacco mosaic virus is so small and simple that it can only proliferate in a cell already hijacked by another virus. And, even though it is a parasite, the satellite tobacco virus is not up to the task of turning a healthy cell's machinery toward its own good. It has to piggy-back on the tobacco mosaic virus in order to reproduce. These unique properties made the satellite tobacco mosaic virus an attractive option for the computer simulation.

A computer program reverse engineered the dynamics of over one million atoms that made up the virus and a small drop of salt water surrounding it. The necessary calculation was achieved using one of the world's fastest and largest computers operated by the National Center for Supercomputing Applications (NCSA). The computer program then provided an unprecedented view into the dynamics of the virus. The computational biologists at the Beckman Institute also collaborated with crystallographers from the University of California at Davis.

Researchers on this project said developing this deeper understanding of the mechanistic properties of viruses could not only contribute to public health, but also aid in the creation of artificial nanomachines made of virus capsids.

"The study followed the life of the satellite tobacco mosaic virus for only a very brief time. Nevertheless, it elucidated the key physical properties of the viral particle as well as provided crucial information on its assembly," Schulten said. "It may still be a long time until we can simulate a dog wagging its tail in the computer, but a big first step has been taken to 'test fly' living organisms. Naturally this will assist modern medicine."