Matching Items (2)
Filtering by
- Creators: Beckstein, Oliver
Description
How water behaves at interfaces is relevant to many scientific and technological applications; however, many subtle phenomena are unknown in aqueous solutions. In this work, interfacial structural transition in hydration shells of a polarizable solute at critical polarizabilities is discovered. The transition is manifested in maximum water response, the reorientation of the water dipoles at the interface, and an increase in the density of dangling OH bonds. This work also addresses the role of polarizability of the active site of proteins in biological catalytic reactions. For proteins, the hydration shell becomes very heterogeneous and involves a relatively large number of water molecules. The molecular dynamics simulations show that the polarizability, along with the atomic charge distribution, needs to be a part of the picture describing how enzymes work. Non Gaussian dynamics in time-resolved linear and nonlinear (correlation) 2D spectra are also analyzed.
Additionally, a theoretical formalism is presented to show that when preferential orientations of water dipoles exist at the interface, electrophoretic charges can be produced without free charge carriers, i.e., neutral solutes can move in a constant electric field due to the divergence of polarization at the interface. Furthermore, the concept of interface susceptibility is introduced. It involves the fluctuations of the surface charge density caused by thermal motion and its correlation over the characteristic correlation length with the fluctuations of the solvent charge density. Solvation free energy and interface dielectric constant are formulated accordingly. Unlike previous approaches, the solvation free energy scales quite well in a broad range of ion sizes, namely in the range of 2-14 A° . Interface dielectric constant is defined such that the boundary conditions in the Laplace equation describing a micro- or mesoscopic interface are satisfied. The effective dielectric constant of interfacial water is found to be significantly lower than its bulk value. Molecular dynamics simulation results show that the interface dielectric constant for a TIP3P water model changes from nine to four when the effective solute radius is increased from 5 A° to 18 A° . The small value of the interface dielectric constant of water has potentially dramatic consequences for hydration.
Additionally, a theoretical formalism is presented to show that when preferential orientations of water dipoles exist at the interface, electrophoretic charges can be produced without free charge carriers, i.e., neutral solutes can move in a constant electric field due to the divergence of polarization at the interface. Furthermore, the concept of interface susceptibility is introduced. It involves the fluctuations of the surface charge density caused by thermal motion and its correlation over the characteristic correlation length with the fluctuations of the solvent charge density. Solvation free energy and interface dielectric constant are formulated accordingly. Unlike previous approaches, the solvation free energy scales quite well in a broad range of ion sizes, namely in the range of 2-14 A° . Interface dielectric constant is defined such that the boundary conditions in the Laplace equation describing a micro- or mesoscopic interface are satisfied. The effective dielectric constant of interfacial water is found to be significantly lower than its bulk value. Molecular dynamics simulation results show that the interface dielectric constant for a TIP3P water model changes from nine to four when the effective solute radius is increased from 5 A° to 18 A° . The small value of the interface dielectric constant of water has potentially dramatic consequences for hydration.
ContributorsDinpajooh, Mohammadhasan (Author) / Matyushov, Dmitry V (Thesis advisor) / Richert, Ranko (Committee member) / Beckstein, Oliver (Committee member) / Arizona State University (Publisher)
Created2016
Description
Na+/H+ antiporters are vital membrane proteins for cell homeostasis, transporting Na+ ions in exchange for H+ across the lipid bilayer. In humans, dysfunction of these transporters are implicated in hypertension, heart failure, epilepsy, and autism, making them well-established drug targets. Although experimental structures for bacterial homologs of the human Na+/H+ have been obtained, the detailed mechanism for ion transport is still not well-understood. The most well-studied of these transporters, Escherichia coli NhaA, known to transport 2 H+ for every Na+ extruded, was recently shown to bind H+ and Na+ at the same binding site, for which the two ion species compete. Using molecular dynamics simulations, the work presented in this dissertation shows that Na+ binding disrupts a previously-unidentified salt bridge between two conserved residues, suggesting that one of these residues, Lys300, may participate directly in transport of H+. This work also demonstrates that the conformational change required for ion translocation in a homolog of NhaA, Thermus thermophilus NapA, thought by some to involve only small helical movements at the ion binding site, is a large-scale, rigid-body movement of the core domain relative to the dimerization domain. This elevator-like transport mechanism translates a bound Na+ up to 10 Å across the membrane. These findings constitute a major shift in the prevailing thought on the mechanism of these transporters, and serve as an exciting launchpad for new developments toward understanding that mechanism in detail.
ContributorsDotson, David L (Author) / Beckstein, Oliver (Thesis advisor) / Ozkan, Sefika B (Committee member) / Ros, Robert (Committee member) / Van Horn, Wade (Committee member) / Arizona State University (Publisher)
Created2016