3-15: Computational approaches to understanding the complex multi-modular enzyme CbhA from Clostridium thermocellum

Fungi and bacteria have developed sophisticated glycoside hydrolases to degrade polymeric carbohydrates. Clostridium thermocellum uses a consortium of enzymes assembled on a protein scaffold to degrade cellulose. The family 9 enzyme, CbhA, from C. thermocellum has an unusually complex construct with 7 modules including: two carbohydrate binding modules, 2 fibronectin-like modules, a family 9 catalytic module, an immunoglobulin-like module and a dockerin. The complexity of this enzyme appears to be important in the way C. thermocellum degrades cellulose using cellulosomes.  In an effort to understand why this enzyme is so complex, we use several molecular simulation techniques including molecular dynamics and normal mode analysis to investigate the actions of these modules, including hydrolysis, disruption, and binding. Such simulations are also useful for hypothesizing the synergistic effects of these modules on one another at the molecular level.