Laboratory of Molecular & Thermodynamic Modeling

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Research Projects

Major Facilitator Superfamily of Membrane Proteins: Structure, Binding, and Transport of Substrates and Enzymes

Membrane transport proteins play significant roles in human physiology, drug transport, bacterial resistance to antibiotics, and diseases, such as cystic fibrosis. The major facilitator superfamily (MFS) is a family of membrane transport proteins found in a broad range of organisms from archaea to the human central nervous system. The organic anion transporter (OAT) family is a member of the MFS that transports important pharmaceuticals in humans, such as β-lactam antibiotics, diuretics, angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) and cardiac glycosides . Lactose permease (LacY) and EmrD drug transporter in E. coli are studied as important models for the MFS. Almost all proteins in the MFS contain twelve membrane spanning helices, as does LacY and EmrD, suggesting a similar transport mechanism for other MFS proteins.

Lactose Permease
Lactose Permease
EmrD Drug Transporter

Cholesterol Transport Mechanisms via the Sterol Sensing Protein (Osh4)

The oxysterol binding protein (OSBP) and related proteins (ORP) are essential for eukaryotic and mammalian cell life. One function of the ORPs is to control the sterol levels and composition in lipid membranes.  For yeast, the seven ORPs (or Osh genes) together control the sterol composition, and the deletion of all the Osh proteins results in cell death.  The expression of ORP4 in human cancer cell lines and solid tumors suggests that ORP4 could be used as a tumor marker.  However, it is unclear if ORPs are directly involved in the development of malignant cells. Recently, the crystal structure of Osh4 complexed with several sterols has been determined (Im, Y. J.; Raychaudhuri, S.; Prinz, W. A.; Hurley, J. H. Nature 2005, 437, 154). Our research is to describe the transport or cholesterol from the membrane to Osh4 and investigate membrane tethering with these proteins.

Osh4 with Cholesterol
Osh4 with Cholesterol
Osh4 interacting with membrane
apo-Osh4 on a Membrane (Im et al., 2007)

Gas Hydrates: Natural Energy Source and Storage for CO2 and Hydrogen

Gas hydrates (clathrates) are a solid network of water, forming cavities that encapsolates gas molecules. These are commonly found in pipelines and can plug the flow of natural gas, but also exist in nature within permafrost or the seafloor. Previous work has focused on developing a thermodynamic model for predicting the equilibrium pressures (or temperatures) of gas hydrates. This thermodynamic model along with a mass transfer model for methane hydrates in the seafloor suggests that there are three orders of magnitude more methane in hydrated form than in conventional global reserves. These results also have huge implications for an alternate source of natural gas reserves within the U.S. to reduce dependency on foreign energy sources. Research in this area has three aspects; 1. thermodynamic stability of naturally occurring hydrates, 2. hydrates to sequester CO2 in the seafloor, and 3. hydrogen storage in clathrate and semi-clathrate hydrates.

Global Distriubtiono of Gas Hydrates
Amount of Methane in Seafloor Hydrates
Natural Sample of Gas Hydrate
Natural Seafloor Hydrate (white)