Enzymatic depolymerization of the insoluble cellulose involves the action of cellulases in the removal of the glucose chains from the surface of the crystal structure. Therefore, molecular level understanding of the properties of cellulose that provide resistance to the depolymerization will be helpful in removing the bottlenecks in the enzymatic hydrolysis process. Hydrolysis of semi-crystalline cellulose by cellulase enzymes is a solid-liquid heterogeneous reaction. Such a reaction is strongly affected by the non-reaction resistances caused most notably by the presence of the crystalline structure. These non-reaction factors include: interfacial area; diffusion of enzyme, substrate and product; and adsorption of enzyme onto non-cellulosic components.  Molecular dynamics simulations are employed to study the cellulose-water and cellulose-cellulase systems. Simulation results are used to quantify the non-reaction resistances in terms of the interfacial structure and diffusion in the system.