Two Fold Peptides
In this project we simulate the free-energy surface of globular (project stage 1) and membrane (project stage 2) peptides. Peptides are small proteins (approx. less than 40 Amino Acids), which are often involved in diseases. One such example is the Amyloid beta protein, where parts are implied in the occurrence of Alzheimer’s disease. A protein is synthesized (i.e. stuck together out of blocks of Amino Acids) in the Ribosome (another big protein). After it exits the Ribosome as a large string of Amino Acids, it often folds all by itself into a usually distinct 3D structure in which it carries out its work. For some proteins however something goes wrong during the folding stage and they end up in another conformation, which does not work. They are usually degraded (destroyed) by your body and nothing happens. Sometimes they end up in another conformation, in which they aggregate. They stick together and form different constructs, which can be the cause of disease (Caution this link is a bit disgusting!). In this project, we want to not only investigate the native conformation, which we did quite often on BOINC already, but also check, whether and how often the investigated peptides end up in another conformation, which might be disease related.
In project stage 1, we prepared the reference protein to start its simulation at three distinct points: The sheet conformation, the helical conformation (zwei Bilder) and the unfolded conformation. Every 500 steps, we measure the conformational distance towards the sheet and the helical conformation. Using this, we can construct a map of all the possible states the peptide can reside in (further information). Depending on how often the protein is able to reach one state from the other, we can say, which conformation is more stable than the other. Usually one conformation will be more stable than the other. For the reference protein both locations should be about evenly stable. CPUs will run one simulation at a time, GPUs will run 100 simulations at a time.
In project stage 2, we will conduct this simulation in both a cellular and a membrane environment. This is important, because some proteins only misfold and aggregate, when they pass through a membrane. In project stage 2, we will also include the first disease implied peptide sequences, where the actual native and misfolded conformations are unknown.