Cellobiohydrolase I (CBH 1) from Trichoderma reesei is one of the most active enzymes in the hydrolyzation of cellulose. CBH 1 is a multi-domain enzyme, consisting of a large catalytic domain containing an active site tunnel and a small cellulose binding module joined to one another by a 27 residue linker peptide, that is believed to hydrolyze cellulose in a "processive" manner. However, the exact mechanism of the depolymerization of cellulose by CBH I is not fully understood. In this work we have performed molecular dynamics simulations that focus on determining the role and function of the linker peptide. Although the sequence of the linker peptide is known and it has been shown that the linker plays an important role in enzymatic activity during cellulose hydrolysis, the spatial conformation adopted by the linker domain is yet to be determined. We probe this through molecular dynamics simulations in which the motion and conformation of the linker adsorbed on a cellulose surface in an aqueous environment are monitored. Potential of mean force calculations have been performed to compute the free energy of the linker as a function of linker length. We compare our simulation data with the hypothesis that the linker behaves like a spring that helps the enzyme to move along the cellulose chain. The goal of the simulations is to help elucidate the fundamental relationship between the structure of the linker and catalysis process of the enzyme, and to provide insight into designing more effective enzymes for the conversion of biomass.

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