Protein dynamics and function
Many biological processes, including enzymatic catalysis and ion permeation through ion channels, result from property averages over a conformational space that spans disparate time and length scales.This structural and dynamical heterogeneity obscures our understanding and limits our ability to provide mechanisms that rationalize macromolecules' observed behavior at the macroscopic scale.
The Welborn group uses electric fields as metrics to understand the role of protein flexibility in catalysis and ion transport. In particular, we seek to reconcile protein dynamics with the seemingly contradictory electrostatic preorganization theory.
Macromolecular function is directly linked to the motion of charged particles, from electrons in the breaking or formation of bonds to ions or ionic complexes in charge transport and signal transduction. Intrinsic electric fields are very sensitive to the geometry of the system. This implies that conformational motions in proteins will cause a change in the orientation and magnitude of these fields. The Welborn group specializes in electric field calculations, with the overall goal to derive a rigorous structure to function relationship for proteins and investigate the effect of dynamic allostery, the process by which macromolecular dynamics control function.
Schematic of the change in the magnitude and orientation of electric fields due to small changes in the geometry of a hypothetical system. Dynamic allostery induces both small and large geometric changes, which can be characterized with electric fields.