Disque Hall 919, S. 32nd Street and Chestnut Street, Philadelphia, PA 19104
Physics Colloquium: "Confined Water Molecules Used as a Template for Drug..."
Thursday, October 16, 2014
3:30 PM-4:30 PM
Giacomo Fiorin, PhD, Temple University
Confined Water Molecules Used as a Template for Drug Design and as a Tool to Study the (Dis)assembly of Human Skin
Water is the smallest molecule in biology, but not necessarily the best understood. In confined environments, for example within membrane
channels, one cannot distinguish easily between disordered water molecules that make up the solution, and ordered ones that are an integral part of a large biomolecular complex. Computation is usually needed to perform such distinction, for example by molecular dynamics simulations. The first part of this colloquium illustrates a study of the M2 proton channel from the influenza A virus: M2 is a tetrameric bundle of alpha-helices, whose
central pore is blocked most efficiently by aklyl-ammonium molecules. Confined water clusters impose significant constraints on the molecular
design of the inhibitors, by dictating both the position of the ammonium ion and the size and shape of the hydrophobic scaffold. The second part
illustrates a simulation study of the multilamellar lipid matrix of the stratum corneum, the outer layer of mammalian skin. The disparity in the molecular lengths of the skin's lipids creates a coexistence of different spacings in the multilamellar structure. Water molecules amplify these differences by coalescing into nanometer-size droplets, analogous to the larger lacunar spaces that can be observed by cryo-microscopy. The interfacial tension between water and lipids governs the equilibrium structure over a wide range of humidity and pH, as shown by a direct calculation of the configurational entropy. This model can be used to predict the permeation of harmful chemicals, or as a basis to design simpler delivery systems for current medications.
Brigita Urbanc, Associate Professor