Dynamics and Regulation of Cytoskeletal Proteins
The application of molecular dynamics (MD) simulations to improve our understanding of the dynamics, and hence, function and regulation of cytoskeletal proteins. Microtubules and kinesin motor proteins play a critical role in the cytoskeleton of the cell. They provide structural support, facilitate cellular transport, and are involved in beating of cilia and flagella, and in separation of chromosomes during the cell cycle. The importance of tubulin dynamics as a vital therapeutic target is exemplified by the widely prescribed paclitaxel (Taxol), an anti-cancer drug that prevents cancer cells from undergoing cell division by arresting tubulin dynamics. Furthermore, the importance of understanding the structural, dynamical, and functional aspects of kinesin motor domains and their modifications is demonstrated by efforts in developing small-molecule inhibitors as antimitotic therapeutic agents in various cancers. However, despite strong conservation of the motor domain across the kinesin superfamily, how various kinesins have tailored their motility characteristics to best meet their functional needs in cells remains unclear.