Mathematical Biology Seminar Jessica Swanson , U of U Chemistry Wednesday, March 22, 2023 3:05pm in LCB 225 Multiscale Kinetic Modeling of Biomolecules: The Challenge of Time-Resolved Data Integration (+Lassos) Abstract: Most biomolecular processes of interest, including ion transport, motor proteins and enzymatic reactions, involve multiple rare event transitions that are crossed by an ensemble of molecules according to Boltzmann statistics. The consequence of this, is multiple mechanistic pathways and heterogeneity at the single-molecule level that is lost in ensemble averages. In this talk, I will explain the kinetic modeling methods we are developing to map out these mechanistic pathways and untangle the kinetic selection that ultimately determines mechanism. I?ll describe how kinetic selection, as opposed to thermodynamics, in fact controls fascinating processes like kinetic proofreading. I'll also demonstrate the value of kinetic modeling with the Cl-/H+ exchange mechanism in the ClC-ec1 antiporter, where we uncover not only the mechanism, but also how the mechanism changes under varying conditions of pH and voltage. Moving forward, we hope to address a central challenge in kinetic modeling, which is identifying the correct solution space, by integrating time-resolved experimental data. Although promising, this will be a challenging mathematical and algorithmic feat. Lastly, I will briefly introduce a geometric curiosity we have encountered in folding lasso peptides into knotted scaffolds.