Scientists are improving cellulose conversion to ethanol using "virtual molecules" to show how the enzyme complex may change shape. The enzyme can straddle a broken cellulose chain, gaining a crucial foothold to digest cellulose into sugar molecules, which can then be fermented into ethanol. Image courtesy of Ross Walker and Amit Chourasia, SDSC, and Michael Crowley and Mark Nimlos, NREL

Termites and fungi already know how to digest cellulose, but the human process of producing ethanol from cellulose remains slow and expensive. The central bottleneck is the sluggish rate at which the cellulose enzyme complex breaks down tightly bound cellulose into sugars, which are then fermented into ethanol.

To help unlock the cellulose bottleneck, a team of scientists conducted molecular simulations at the San Diego Supercomputer Center, based at the University of California at San Diego, California, U.S. By using "virtual molecules," they have discovered key steps in the intricate dance in which the enzyme acts as a molecular machine-attaching to bundles of cellulose, pulling up a single strand of sugar, and putting it onto a molecular conveyor belt where it is chopped into smaller sugar pieces.

"By learning how the cellulase enzyme complex breaks down cellulose we can develop protein engineering strategies to speed up this key reaction," said Mike Cleary, who is coordinating SDSC's role in the project. "This is important in making ethanol from plant biomass a realistic 'carbon neutral' alternative to the fossil petroleum used today for transportation fuels."

The results were reported in the April 12 online edition of the Protein Engineering, Design and Selection journal, which also featured visualizations of the results on the cover.

"Our simulations have given us a better understanding of the interactions between the enzyme complex and cellulose at the molecular level," says first author Mark Nimlos, a senior scientist at NREL. "The computer model showed us how the binding portion of this enzyme changes shape, which hadn't been anticipated by the scientific community."

To the scientists, the simulation is like a stop-motion film of a baseball pitcher throwing a curveball. In real life the process occurs far too quickly to evaluate visually, but by using the supercomputer simulations to break the throw down into a step-by-step process, the scientists can see the precise details of the role of velocity, trajectory, movement and arm angle. To undertake the large-scale simulations, the researchers used the CHARMM (Chemistry at HARvard Molecular Mechanics) suite of modeling software.

According to the researchers, an accurate understanding of the key molecular events required the simulations to run for some six million time steps over 12 nanoseconds (a nanosecond is one billionth of a second) in order to capture enough of the motion and shape changes of the enzyme as it interacted with the cellulose surface.

You can view movies and images online of molecular machines converting cellulose to biofuel.

This story originally appeared as an 'SDSC Nugget' on the San Diego Super Computing Web site. Adapted with permission.

- Paul Tooby, San Diego Supercomputer Center