MOLECULAR DYNAMICS SIMULATIONS ON CBH I WITH A CELLULOSE STRAND INSIDE THE CATA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cellulosic ethanol is an optimistic substitute for fossil fuels and its efficient production from renewable sources will be essential in securing the future prosperity of the United States. Currently industrial scale production of ethanol from biomass utilizes acid catalyzed hydrolysis of insoluble cellulose. This approach is both limited in scalability and presents a number of environmental issues. A more environmentally friendly process, hydrolysis by cellulase enzymes, is a enticing goal. However, the massive application of such a process is hindered by the low turnover rates of the enzyme's catalytic pathway. An understanding of the catalytic mechanism of cellulase is a prerequisite of what will ultimately be a long term and ambitious project in protein engineering. We have been the first group to utilize molecular dynamics simulations to study the complete CBH I enzyme (including the catalytic, linker and binding domains in a single simulation) on an intact crystalline cellulose microfibril in solution. This initial work was conducted using SDSC resources and part of the results have recently been accepted for publication in the journal Cellulose. We also want to study the behavior of the protein when a strand of cellulose is threaded into the catalytic tunnel in the hope that it will reveal the catalytic mechanism and be used to identify important amino acid residues involved in such a process. Such knowledge will be useful for mutagenesis experiments to produce more active proteins. Here we are requesting a Development Allocation of 30,000 SUs to carry out initial benchmarking and testing of the planned simulations using the CHARMM software. This initial study will form the basis of a MRAC proposal that we plan to submit in the near future.