Niemann-Pick type C is a genetic disorder caused by mutations in NPC1 and NPC2 genes. The proteins coded by these genes work as a team to transfer cholesterol from lysosomes, the waste disposal systems of the cell. Malfunction of either of these proteins causes accumulation of cholesterol and other lipids. Individuals affected suffer from difficulty coordinating movements, poor muscle tone, liver disease, lung disease, and problems with basically all organs. Niemann-Pick disease is fatal and patients usually die before age of five. Also lysosomal membrane lipids have some role in cholesterol transportation. In this project that role is studied using molecular dynamics. This project is the topic of my masters thesis, which should be finished soon.
The permeability and flip-flop-properties of lipid bilayers containing oxysterols was studied using molecular dynamics simulations. The two chosen oxysterols were 27-hydroxy-cholesterol (HCH) and 7β-hydroxycholesterol (BCH). Bilayers containing these oxysterols were compared with bilayer containing non-oxidised cholesterol (CHOL) and bilayer without any sterols (pure POPC). Water molecules and oxalate-ions (OXA) were pulled through bilayers and free energy profiles were measured using umbrella sampling. Gromacs 4.6 and OPLS-AA force field were used in all simulations.
HDL (High Density Lipoprotein) is the smallest of the five major groups of lipoproteins which play an essential role in plasma lipid transport. HDL transports cholesterol from blood vessels to liver for excretion. As this “reverse cholesterol transport” decreases the risk of cardiovascular disease, HDL acting as a carrier of cholesterol is often called “good cholesterol”. Electrostatic properties of small particles like HDL affect their stability and interactions with for example lipid membranes. In this project the goal was to use molecular dynamics simulation to measure the zeta-potential of HDL particle. I also wrote my bachelor’s thesis about this topic.