Understanding the Structural Differences Between Psychrophilic and Thermophilic Enzymes: A Molecular Dynamics Study

Industrial use of enzymes has grown at a tremendous rate. The global market for industrial enzymes is predicted to reach $7 billion by 2018. This is not surprising, given enzymatic catalysis results in high yields, low cost and is environmentally friendly compared to many conventional chemical catalysts. A wide range of industrial markets, such as food industry, textile industry, pharmaceuticals, deployable biosensors and production of biofuels are exploring enzymatic catalysis. These diverse markets demand more robust enzymes which can tolerate environments ranging from low to high temperatures. However, most enzymes are inactive and denature at such extreme conditions.

Extremophile proteins – that include thermophilic and psychrophilic proteins are being investigated as enzymes for extreme temperatures. Thermophilic and psychrophilic proteins refer to enzymes that are active at high and low temperatures respectively but not at ambient temperatures. Thermophilic enzymes are more stable at high temperatures while psychrophilic enzymes tend to have shorter lifetimes and tend to be less stable at ambient temperatures. The underlying reasons for the differences in the range of the temperatures that these enzymes are active is not yet understood. Studies have suggested that the active site flexibility of psychrophilic enzymes provides their high activity at low temperatures. In contrast, the loss of flexibility helps thermophilic enzymes retain stability at high temperatures. We test this hypothesis through large-scale all-atom molecular dynamics (MD) simulations. Specifically, we perform simulations of G. thermocatenulatus (GTL) – a thermophilic enzyme and P. lipolyticum (M37L) – a psychrophilic enzyme in a range of temperatures. We investigate the differences in the global and local flexibility, specifically near the active site in both enzymes. In our talk, we will present these results and comment on their implications for designing enzymes with a broader range of stability and activity.