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Protein dynamics and allostery

Many biological processes, including enzymatic catalysis and ion permeation through ion channels, rely on allosteric regulation. This allosteric control stems from a change (binding of a drug, mutation, ...) at a site other than the active site that modifies the shape and activity of the protein. However, the nature and extent of the coupling between the active and allosteric sites is not well understood.

 

The Welborn group uses intrinsic electric fields as metrics to understand the role of protein flexibility in allosteric regulation of 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.

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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.