Computer simulates protein creation

The lab simulated how a cellular machine called a ribosome follows genetic instructions to construct a protein, a complex molecule, out of its component parts -- amino acids. With 768 processors of LANL's 8,192-processor ASCI Q machine running for about 260 days, the researchers created a film of the process. Previous views had shown only static snapshots.

"Experiments have been able to come up with snapshots of the ribosome. We're trying to create a movie of what happens between those snapshots," said Kevin Sanbonmatsu, a molecular biologist and the project's principal investigator.

The movies could be significant for research into antibiotic medicines. Antibiotics work by gumming up the ribosomes, and a film showing a ribosome's function could show a larger range of targets than static images, he said.

The task wasn't simple. Researchers had to model the physical interactions of each of 2.64 million atoms -- about 250,000 in the ribosome itself, but most for water molecules inside and outside it. The simulation resulted in a movie that is 20 million frames long, he said.

In reality, however, the ribosome behaviour that they simulated takes only 2 nanoseconds, or 2 billionths of a second.

Ribosomes are fundamental to life. "Ribosomes are thought to be one of the oldest artefacts from the beginning of life that we can study today," Sanbonmatsu said. "If you compare the genetic sequence of ribosomes in humans and in bacteria, it's very, very similar. Most of the core of the ribosome is identical in every organism that's ever been sequenced."

The new research illuminates previously known biological mechanisms that begin with genetic information stored in DNA. That information is transferred into biological reality through a multi-step process. Proteins -- complex molecules such as haemoglobin to transfer oxygen in blood, or insulin to help metabolise sugars -- are made of a chain of amino acids, and DNA encodes the order of the amino acids for each type of protein.

To create a protein, the dual strands of DNA are temporarily unzipped to permit the creation of a single-strand copy of the genetic information, called messenger RNA. The messenger RNA is then processed by the ribosome.

The ribosomes connect, in the appropriate amino acid, to the growing chain that forms each protein. Amino acids are carried into this molecular factory by tiny packages called transfer RNA.

What the LANL researchers think they've found is a corridor in the ribosome that screens out the inappropriate amino acids from the sea of transfer RNA.

"What we've discovered in the simulation is that this is a possible mechanism to accept or reject transfer RNA," Sanbonmatsu said. "This corridor acts like a gate."

Next, the researchers will try to experimentally verify the simulation's results, simulate antibiotic interactions with the ribosome and model how the ribosome moves step-by-step along the messenger RNA strand.

This simulation used six times as many atoms as the previously largest model known. That scale is significant, Sanbonmatsu noted.

"This allows us to look at more realistic and physically relevant systems," he said. A ribosome itself is a "huge complex of messenger RNA and 50 proteins. Most things in cells are complexes of RNA and proteins."

Such simulations are increasing dramatically in sophistication. A machine called Blue Gene/L at LANL's sister lab, Lawrence Livermore National Laboratory, is scheduled for a ceremonial unveiling on Thursday. Blue Gene/L is currently the world's fastest supercomputer, sustaining calculations at the rate of 136.8 trillion per second compared to 13.8 trillion for ASCI Q. Blue Gene/L performance is expected to roughly double this year as all its processors are installed.