Using computer simulations to study biological problems
Cholesterol is a crucial component of mammalian cellular membranes, making up a significant portion (25-40 mol%) of the plasma membrane. Eukaryotic cells are thought to contain lipid rafts, which are small, dynamic domains enriched in cholesterol, sphingomyelin, and membrane proteins. Lipid rafts could mediate cell signaling, lipid and protein trafficking, and pathogen entry. How these molecules interact is paramount for understanding eukaryotic life, and they have been implicated in many important diseases, including cancers, diabetes, Alzheimer’s disease, HIV entry, and atherosclerosis.
Drew Bennett is using Molecular Dynamics (MD) computer simulations to probe the interaction between cholesterol and phospholipids at sub-nanoscale resolution. MD simulations involve two basic steps: determining the energy of the system and the resulting force on each atom, then updating the positions based on Newton’s equations of motion.
These steps are repeated millions of times and require the use of powerful supercomputers to produce a short (100s of nanoseconds) movie or trajectory of the molecules’ thermal fluctuations. From the trajectory, researchers can determine macroscopic properties through statistical mechanics and compare them to experimentally observable properties. MD simulations provide a novel view of membrane systems, with atomistic details of the dynamic behavior of single molecules - generating structural, mechanistic, kinetic and thermodynamic data.