(520c) How the Walls Come Crumbling Down: Elucidating Mechanisms of Cellulose-Active Enzymes Using Molecular Simulation

The microbial degradation of plant matter is one of the most important components of the global carbon cycle. Beyond the natural importance of biomass turnover, plant cell wall polysaccharides also offer significant promise as a renewable resource for the sustainable production of fuels and chemicals to partially offset mankind’s fossil fuel usage, but the cost for using natural enzyme systems in industrial contexts remains high. Understanding the enzymatic mechanisms of cellulose deconstruction is key need to engineer enhanced biocatalysts, and computer simulation offers a powerful, complementary tool to experimental enzyme engineering approaches. In this talk, I will describe research efforts from our group aimed at understanding rate-limiting steps in cellulase enzyme action using a wide variety of computational methods including absolute ligand binding free energy calculations, transition path sampling, and QM/MM simulations. In concert with experimental measurements, computation has enabled the identification of the rate-limiting step in one of the most abundant and widely used cellulases in biofuels applications, and thus highlights a target for experimental protein engineering. I will also briefly highlight computational work from our group on understanding the molecular mechanisms of cellulose biosynthesis.