Neural disorders research experiments
Uncovering the role of membrane lipids in modulating enzyme activity
WU tags: FAAH
Lipids and the membranes they form are one of the basic functional units of all life, from bacteria up to humans. They have historically received less reseach attention than other biomolecules because they were seen primarily as scaffolding on which proteins, DNA, and RNA could function and segragate. Lately, however, it is becoming clear that lipids and their composition in membranes play key functional roles, facilitating or attenuating various processes like signaling and protein activity. In a recent work published in Biochemical Journal, we provide a mechanistic explanation of how membrane lipids modify the activity of the enzyme Fatty Acid Amide Hydrolase (FAAH) by facilitating binding. Additionally, we show the unbiased binding of the lipid andandamide to the enzyme. On the right you can see a video showing the binding process. This enzyme plays an essential role in terminating signaling in the endocannabinoid system, and is important for a wide spectrum of biological function, including memory, immune response, hunger and pain.
This research was conducted in collaboration with Dr. Enrico Dainese from the University of Teramo, Italy.
- E. Dainese, G. De Fabritiis, A. Sabatucci, S. Oddi, C. Angelucci, C. Di Pancrazio, T. Giorgino, N. Stanley, B. Cravatt, and M. Maccarrone, Membrane lipids are key-modulators of the endocannabinoid-hydrolase FAAH, Biochem J. 2014 Feb 1;457(3):463-72. PDF can be found here
Molecular simulations of the D2 Dopamine receptor under physiological ionic strength conditions
WU tags: JAN
Sodium ions have been shown to play an important role in the binding of antipsychotic drugs to the D2 Dopamine receptor. Understanding the sodium-induced mechanism is of great interest for future drug design in the treatment of schizophrenia.
By means of molecular dynamics we simulate the mobility of sodium ions and its effect on the dynamic properties of the D2 receptor under physiological ionic strength conditions.
GPUGRID technology allows us to handle an all-atom system in which D2 receptor is embedded in a membrane bilayer with a total of 61,000 atoms and accelerates the computational performance up to microseconds.
Research conducted in collaboration with Dr. Jana Selent from Universitat Pompeu Fabra.
- J. Selent, F. Sanz, M. Pastor and G. De Fabritiis, Induced Effects of Sodium Ions on Dopaminergic G-Protein Coupled Receptors, PLOS Computational Biology, 6, e1000884 (2010)