Molecular mechanics computer simulations are being used to model the interaction of the multi-domain processive exocellulase CBH I from T. reesei, a biological "nano-machine," interacting with a cellulose microfibril, in order to understand the mechanism of hydrolysis as a guide in designing improved mutant enzymes with enhanced turnover rates. This work is basic to improvi"g biomass con"ersion, the effort to convert cellulose in materials such as wood chips and corn stover to alcohol for use as a transportation fuel, a national research priority.

The world’s supply of non-renewable fossil fuels is being rapidly exhausted, particularly as the largest developing countries begin to consume proportionally more oil. Part of the fuel needed for transportation could be replaced with ethanol produced from renewable biological waste materials containing cellulose if the polysaccharide chains could be broken down into the constituent glucose repeat units for use in industrial fermentation. Fungal and bacterial enzymes to effect this hydrolysis are known but have inconveniently slow turnover rates. Understanding how these systems work would allow the efficient design of improved cellulases via protein engineering, helping make this process industrially feasible.

Molecular mechanics computer simulations have been used to study the mechanisms of several cellulases on the atomic and molecular level, in order to understand the functions of specific residues in the target enzymes, how the insolubility and nano-structure of the substrate limit the process, and the role played by water in affecting the rate. Similation computer studies have been used to study the structure of the cellulose substrate itself to help understand why it is so resistant to hydrolysis.

Computer simulations have been used to model the action of the cellulase nanomachine CBH I from T. reseii interacting with its cellulose substrate. Also, similar modeling has been used to understand the structure of cellulose itself and how this impacts the activity of the cellulase upon it. These studies are providing the information needed to design improved methods of enzymatic conversion of waste material such as wood chips, grasses, and corn stover to liquid alcohol for use as a fuel, replacing imported non-renewable petroleum with renewable domestic supplies and enhancing the value of agricultural crops. This is a national reaserch priority mentioned by President Bush in his past two State of the Union addresses.

Federal Department of Energy funding as a subcontract from the National Renewable Energy Laboratory