Modeling of Conformational Transitions in Membrane Proteins with Coarse-Grained Methods

Sammanfattning: Understanding the dynamics of proteins is crucial in order to understand life on a molecular level. In this Bachelor’s thesis large scale motions of the membrane protein SERCA has been investigated with coarse-grained methods. The goal was to find certain places in the structure where mutations could alter and affect the functionality of the protein, possibly leading to disease. The protein was modeled with an elastic network model and simulated with Langevin dynamics. Data from the simulations was used to calculate all the places were formation of stabilizing salt bridges were possible and these were then compared with mutations found in real cancerous cells. Promising results were obtained but need to be investigated further with more sophisticated methods before any conclusions can be drawn regarding their significance for the protein functionality. Likewise, the use of elastic network models together with Langevin dynamics showed to be a good alternative to sample large conformational changes in proteins.