This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We propose to study the interaction of a key cellobiohydrolase I (CBH I)with its microcrystalline cellulose substrate using CHARMM. This enzyme isnow recognized as a molecular machine because it must process along asingle strand of cellulose (a cellodextrin), hydrolyzing b-(1,4) glycosidiclinkages to liberate cellobiose. Cellobiose, a disaccharide, can behydrolyzed enzymatically to glucose, a sugar suitable for many fermentativeprocesses. The Department of Energy (DOE) Office of the Biomass Program(OBP) is currently funding applied research that leads to technologiessupporting the production of fuel ethanol and other important chemicalsfrom renewable resources. CBH I is the pivotal enzyme in thisbiodegradative process, and, as such, the proposed cellulase modeling atSDSC will generate critical data needed for new research strategies usingintegrated mutational biochemistry and computer science.In addition, the size of the proposed molecular simulation far exceeds anyexisting study. We propose to study the interaction of the complete CBH Ienzyme with a realistic microfibril of cellulose in the presence ofexplicit water molecules. All three components have important functions inthe processive action of CBH I, and require modeling a system of nearly800,000 atoms! As such, this project should significantly expand the rangeof biological systems that can be studied with molecular dynamics. Thus,this project will be of general interest to the scientific community. Thiseffort requires the participation of numerous professionals includingbiochemists (NREL), carbohydrate chemists (Cornell), software developers(Scripps), and computational scientists (SDSC). Thus, we propose a highly collaborative study involving a unique scientificteam to better understand this critical enzyme and to continue to improvethe performance of CHARMM on High Performance Computers (HPC) available atSDSC. DOE OBP funds the PI and the CoPI in this study; however, becausethis work is not linked to the Office of Science, access to DOE HPC systemsis not available. Also, the computational facilities at NREL areinsufficient for this task. We conclude that the proposed calculations canonly be performed at an NSF center, like SDSC.
Showing the most recent 10 out of 292 publications
