Using computer simulations to study biological problems
Cells have elaborate mechanisms to transport substances such as nutrients and drugs across the cell membrane that forms a barrier between the inside and outside of a cell. ATP-Binding Cassette Transporters form a large class of membrane proteins across all forms of life that play important physiological roles, including nutrient uptake in bacteria, drug resistance in cancer cells, and regulation of processes involved in cystic fibrosis and diabetes. The chemical hydrolysis of ATP, a source of energy, provides the power for ABC transporters to drive transport, but it is not clear how this common mechanism works exactly.
In this project, computer simulations on powerful parallel supercomputers are used to better understand the structural changes that occur during transport. The coupling between ATP hydrolysis, which happens in two domains outside the cell membrane, to motions inside the cell membrane is an important problem. Experimental methods have provided snapshots of structures of ABC transporters, and many experiments have provided a wealth of biochemical data. The goal of this project is to understand the mechanism of ABC transporters in more detail. This knowledge might be useful in the long term to develop more effective drug therapy in certain forms of cancer, cystic fibrosis, and other diseases related to ABC transporters.