Renewable Energy: BioEthanol Understanding the Processivity of Cellobiohydrolase Cel7A (CBH I) Michael Crowley National Renewable Energy Laboratory

Improving the efficiency of producing ethanol from lignocellulose is a vital step in reducing our nation's dependence on foreign oil. There is a class of glycoside hydrolase enzymes called cellulases that are thought to decrystallize and processively depolymerize cellulose using biochemical processes that are largely not understood. Prominent among the cellulases is the cellobiohydrolase found in Trichoderma reesei, CBH I. These enzymes are truly protein machines. They provide a direct link between the important biopolymer found in plant matter (cellulose) and sugars that can form the basis of many renewable fermentation technologies. Understanding the mechanisms involved and improving the efficiency of this hydrolysis process through computational models and protein engineering presents a compelling grand challenge.

This project will expand the capabilities of existing computational tools to investigate the processivity mechanism of CBH I in cellulose hydrolysis. Carefully designed molecular dynamics (MD) simulations of the binding and catalytic domains of CBH I will be conducted with various substrate configurations, solvation models, and thermodynamic protocols. Some of these simulations can be done with existing MD software (CHARMM, Amber) running at terascale. Many, however, will require significant modification of codes and algorithms to efficiently utilize petascale hardware.

The result of this multidisciplinary effort will be fundamental advances in our understanding of the action of critically important microbial cellulases. An additional benefit of this work will be the development of MD codes that can efficiently utilize terascale and petascale systems, not just for classical MD simulations, but also for more advanced methods, including Umbrella Sampling, Steered Molecular Dynamics, and Quantum Mechanical/Molecular Mechanical simulations of systems the size of cellulose-degrading enzymes acting on cellulose.

Science Application: Computational Biology

Project Title: Understanding the Processivity of Cellobiohydrolase Cel7A (CBH I)

Principal Investigator: 2008: Michael Crowley (2007:Michael Himmel)
Affiliation: National Renewable Energy Laboratory

Participating Institutions and Co-Investigators:
National Renewable Energy Laboratory - Michael Himmel, Steven Hammond, Mark Nimlos, Shi-You Ding, Michael Crowley
Oak Ridge National Laboratory - Ed Uberbacher, Brian Davison, Phil LoCascio, Phani Nukala
Cornell University - John Brady, Linghao Zhong
Forest Products Research Lab - Rajai Atalla
Scripps Research Institute - Charles Brooks III
University of California at San Diego - Joseph M. Cleary, Amitava Majumdar, Ross Walker

Funding Partners: Office of Science — Office of Advanced Scientific Computing Research, and Office of Biological and Environmental Research

Budget and Duration: Approximately $1 million per year for five years ¹

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