Many industrially important cellulolytic enzymes, such as CEL7A (also known as cellobiohydrolase 1), natively exhibit numerous glycosylation sites for covalent attachment of N- and O-linked glycans. The presence of such glycans, as well as variations in their chemical structures, can influence enzyme properties such as substrate binding, catalytic efficiency, and thermostability. While the CEL7A sequence manifests four potential N-glycosylation sites, only three of which are typically glycosylated, the extent of glycosylation at each site varies with expression host. For example, yeast systems generally express cellulases that are hyperglycosylated compared to fungi. Both hyperglycosylation and the presence of glycans at particular glycosylation sites have been shown to negatively impact catalytic activity, yet the presence of glycans at alternative sites, including those engineered into the enzymes, have been shown to enhance activity. Furthermore, studies suggest that glycosylation contributes structural integrity that facilitates the functioning of cellulases under harsh reaction conditions, such as high temperature or pressure, that are often preferred during the industrial production of bioethanol. Despite the relationship between enzyme glycosylation and demonstrated cellulolytic functionality, the structural mechanisms by which glycosylation alters enzyme properties remain largely undetermined.Molecular dynamics simulations provide a powerful solution for investigating structure/function relationships in biomolecular systems. Here, a range of CEL7A glycoforms are simulated at high temperature/pressure in order to elucidate the structural role by which glycosylation enhances thermodynamic integrity. Findings are supported by analogous experimental studies of CEL7A under thermal/baric stress. Combining theory with experiment to develop a more comprehensive understanding of glycosylation as a factor controlling cellulolytic enzyme functionality will ultimately enable researchers to exploit glycosylation as a strategy for tuning cellulase efficiency and stability, which can serve to enhance the cost-competitiveness of second-generation biofuels.