259933 QM/MM Metadynamics Analysis of Reaction Thermochemistry and Kinetics for Biomass Processing
We have previously characterized the glycoside hydrolase (GH) mechanism using density functional theory (DFT) calculations. The GH reaction is a key step in breaking down polysaccharides for use in fuels and chemicals. Once it is broken down into simple sugars, it can be used in fermentation and other catalytic processing steps . However, in order to accurately describe the enzyme active site that leads to efficient biocatalysis, we need better methods for including solvation effects in reactions for biomass processing due to the presence of the solvent. We have used Quantum Mechanics/Molecular Mechanics (QM/MM) modeling along with metadynamics to gain more insight into the role of the solvent and active size during enzymatic breakdown of polysaccharides. Using the transition state structures and energies previously found using DFT calculatins in vacuum and continuum solvent models, we have expanded the system to include more of the active site and an explicit description of the solvent. This is particularly important with biomass due to the many conformers with similar energies.
We have used QM/MM simulations in conjunction with the metadynamics method  to evaluate the free energy of reaction for different steps in biomass degradation. We have constructed the minimum free energy path (MFEP) for the xylose-xylanase enzymatic reaction in water at the PM6 and B3LYP//AMBER level of theory. The reaction coordinates were chosen based on our ab initio calculations, and consist of bond distances between atoms involved in the mechanism. Using the full MFEP, we are able to estimate the reactions’ kinetic properties using transition state theory from statistical mechanics. The poster will also present a quantitative comparison between the full DFT (gas phase and continuum) and QM/MM results.
 Dodd and Cann. Enzymatic deconstruction of xylan for biofuel production. GCB Bioenergy (2009) vol. 1 (1) pp. 2-17
 Barducci, A., Bonomi, M. and Parrinello, M. (2011), Metadynamics. WIREs Comput Mol Sci, 1: 826–843. doi: 10.1002/wcms.31
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