By learning how the cellulase enzyme complex breaks down cellulose we can develop protein engineering strategies to speed up this key reaction. This is important in making ethanol from plant biomass a realistic ‘carbon neutral’ alternative to the fossil petroleum used today for transportation fuels.

—Mike Cleary, SDSC

The scientists found that initially the binding part of the enzyme moves freely and randomly across the cellulose surface, searching for a broken cellulose chain. When it encounters an available chain, the cellulose itself seems to prompt a change in the shape of the enzyme complex so that it can straddle the broken end of the cellulose chain. This gives the enzyme a crucial foothold to begin the process of breaking down the cellulose into sugar molecules.

Our simulations have given us a better understanding of the interactions between the enzyme complex and cellulose at the molecular level—the computer model showed us how the binding portion of this enzyme changes shape, which hadn’t been anticipated by the scientific community. These results are important because they can provide crucial guidance as scientists formulate selective experiments to modify the enzyme complex for improved efficiency

—Mark Nimlos, a Senior Scientist at NREL

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 to capture enough of the motion and shape changes of the enzyme as it interacted with the cellulose surface.

This is an extremely long time in molecular terms, and the computation-hungry simulations ran for some 80,000 processor-hours on SDSC’s DataStar supercomputer.

Also participating in the study were Michael Crowley, William Adney, and Michael Himmel of the Department of Energy’s National Renewable Energy Laboratory (NREL); James Matthews and John Brady of Cornell University; Linghao Zhong of Penn State University; as well as Ross Walker, and Giridhar Chukkapalli of SDSC.

The research was partially funded by the Department of Energy’s Biomass Program and the National Science Foundation.

Resources:

• Movies and images of the simulation

• “Molecular modeling suggests induced fit of Family I carbohydrate-binding modules with a broken-chain cellulose surface”; Mark R. Nimlos, James F. Matthews, Michael F. Crowley, Ross C. Walker, Giridhar Chukkapalli, John W. Brady, William S. Adney, Joseph M. Cleary, Linghao Zhong and Michael E. Himmel; Protein Engineering Design and Selection, doi:10.1093/protein/gzm010