Abstract: The transport of small molecules and ions across the membrane of a cell is essential for its survival. This active movement of matter is performed by transporter proteins in the membrane. How these proteins function at the atomic scale has been difficult to understand, despite a number of atomic resolution structures of transporter proteins from X-ray crystallography. I will show how computational methods in combination with experimental techniques can provide unique new insights into the molecular mechanisms of active transport. I will focus on a class of sodium/proton antiporter proteins, whose dysfunction is implicated in a variety of complex diseases, including cancer, cardiovascular pathophysiology, and autism. These secondary active transporters are molecular machines that utilize the free energy in a transmembrane electrochemical gradient of one ionic species to drive energetically uphill transport of the other ion. Molecular dynamics simulations show how conformational changes together with differences of a single proton in the transporter may couple the inward and outward ionic fluxes and thus provide a mechanistic atomic-scale picture of a molecular machine.
Biography: Oliver Beckstein, D.Phil., received his undergraduate degree in physics (Diplom Physik) in 1999 from the University of Erlangen-Nuremberg, Germany and his D.Phil. in Biochemistry in 2005 from the University of Oxford, UK. He was awarded a Junior Research Fellowship at Merton College, Oxford. He worked as a postdoctoral researcher with Tom Woolf at Johns Hopkins University and Mark Sansom in Oxford. He became an Assistant Professor in the Department of Physics and the Center for Biological Physics at Arizona State University in 2012. Dr Beckstein's current work focuses on using computational approaches to understand the molecular mechanisms of fundamental biological processes such as the active transport of matter into and out of the cell. His research group also develops novel computational algorithms and tools and leads the development of the widely used open-source MDAnalysis library http://mdanalysis.org.