About the image: The GABAa receptor is a neuronal ion channel that plays a dominant role in sleep and relaxation processes, by inhibiting electrical signals in the central nervous system. Dr. Brannigan has studied this family of receptors for over five years, but new crystallographic data from structural biologists makes this an especially exciting time for simulations.

About the background: The background contains images of several small molecule modulators of the GABAa receptors and other receptors in this family; the modulators shown here include cholesterol, progesterone, DHEA, propofol, and thyroid hormone (T3).  These neuromodulators bind to multiple sites on the GABAa receptor, and isolating the location, strength, and implications of binding to each individual site is challenging experimentally. We use free energy methods in combination with large scale molecular dynamics simulations to characterize the affinities of a neuromodulator for individual sites. This process is one of the first steps in unraveling the mechanisms by which these modulators function, as well as in designing new synthetic modulators.