Title: Kinetic Selection in Transporters: Teasing Out the Roles of the Electrical and Chemical Gradients
Dr. Swanson is an Assistant Professor of Chemistry at the University of Utah. Prior to that she was at the University of Chicago for 9 years where she researched biomolecular systems, particularly those involving charge transport, with multiscale modeling and simulations. She trained with Andy McCammon as a graduate student and Jack Simons as an NIH Ruth Kirstein Postdoctoral Fellow. Research in the Swanson Group bridges computational biophysics and theoretical chemistry with the development and application of multiscale simulation methods, particularly kinetic modeling, to probe medically and environmentally relevant biological processes at the molecular level. Put simply, her group wants to understand how and why fascinating biological systems work the way they do. The group’s most recent focus is on methanotrophic methane mitigation to address near-term warming.
Electrochemical gradients, such as the proton motive force, play a central role in bioenergetic transformations. Although they are the consequence of one thing—a transmembrane solute gradient—they pack a double punch of energetic driving forces: one due to the dissipative force of a solute moving down its concentration gradient, and the other due to the electrostatic force of any charged species moving in response to an electric field. These two forces are commonly assumed to have an equivalent impact on ion transport due to their Nernstian relationship.
In this work, we challenge this notion, highlighting differences in both the physical influence of the two forces on the transport reaction free energy landscape as well as on the reaction flux through competing reaction pathways. Using multiscale kinetic modeling (MKM) we quantify the influences of both driving forces in the reaction network for coupled Cl–/H+ exchange in ClC antiporters. This allows us to describe for the first time the competing experimental assays for pH-dependent ion flux. Comparing these results to simple model systems reveals a critical role of the lower ion binding site, which has been heavily debated. This work suggests the potential role of ClC-ec1 in bacterial extreme acid response and has broad implications for voltage-driven processes.
Keywords: ion transport, multiscale simulations, kinetic modeling, electrochemical potential, membrane proteins, computational biophysics
Host: Prof. Arun Yethiraj