Recent progress in MD simulations of the CBH I cellulase from T. Reesei bound to cellulose microfibrils

CELL 158

John W. Brady, jwb7@cornell.edu1, Linghao Zhong, luz4@psu.edu2, James F. Matthews, jfm17@cornell.edu3, Michael F. Crowley, michael_crowley@nrel.gov4, Joseph M. Cleary, mike_cleary@nrel.gov4, Ross C Walker, rcw@sdsc.edu5, Mark R. Nimlos, mark_nimlos@nrel.gov4, Charles L. Brooks III6, and Michael E. Himmel, mike_himmel@nrel.gov4. (1) Department of Food Science, Cornell University, Stocking Hall, Ithaca, NY 14853, (2) Pennsylvania State University at Mont Alto, 1 Campus Drive, Mont Alto, PA 17225, (3) Department of Food Science, Cornell Univesity, Stocking Hall, Ithaca, NY 14853, (4) Chemical Biosciences, National Renewable Energy Laboratory, 1617 Cole Blvd Mailstop 3323, Golden, CO 80401, (5) Strategic Applications Computing, San Diego Supercomputing Center, University of California, San Diego, 9500 Gilman Drive #0505, La Jolla, CA 92093, (6) Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI 48109
The conversion of cellulosic biomass to ethanol for use as fuel has become a major priority as the search for liquid fuels from renewable sources becomes more urgent. Enzymatic conversion of cellulose to glucose for use in fermentation is an attractive route to this objective, but turnover rates for natural cellulases are too low to be industrially practical. A principal limiting factor is the insolubility of cellulose. In this context, processive cellulases that successively hydrolyze linkages in a single chain offer a particularly promising approach. Molecular Dynamics (MD) computer simulations have been widely used to study proteins and carbohydrates, including polysaccharides, and can potentially be applied to understanding the mechanism of actions of such enzymes. The large sizes of cellulose polysaccharides cellulases and the long timescales for their motions are serious impediments to modeling such systems in atomistic detail. However, with the advent of massively-parallel computers, simulations not previously feasible become possible, at least in principle. Recent progress in MD simulations of microcrystalline cellulose and its interactions with water and with the CBH I cellulase (Cel7A) from T. reesei will be described. Preliminary investigations of a fibril with a complete CBH I cellulase complex bound to it in an aqueous periodic box have been initiated. A single chain of cellulose from the (100) surface of the fibril is threaded into the active site tunnel of the enzyme. The behavior of the various domains and components of the system will be described along with a discussion of what the results might imply for the mechanism of processivity.
 

Structure and Properties of Cellulosic Polymers, Assemblies, and Nanocomposites
1:00 PM-4:45 PM, Monday, April 7, 2008 Morial Convention Center -- Rm. R07, Oral

Division of Cellulose & Renewable Materials

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008