Dynamic allostery in proteins
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. In some cases, coupling pathways (characterized by residue networks) have been identified, suggesting that allostery occurs through conformational fluctuations. This immediately raises the question of how/whether conformational fluctuations contribute to allostery in environments where protein dynamics are constrained or limited.
Protein dynamics in cold environments
We study allosteric regulation of enzymes in cold environments where equilibrium thermal fluctuations, hence conformational fluctuations, are limited.
Fluctuations in transmembrane ion channels
We develop methods to model the dynamics of voltage-dependent sodium channels embedded in a biological membrane. Our goal is to elucidate the connections within the channel responsible for allosteric regulation. Understanding the detailed mechanisms behind allostery in the ion channels responsible for the transmission of action potentials has application to drug design and the remediation of neurodegenerative diseases.
Kinetic model of the eukaryotic voltage-dependent sodium channels where the transition between states is driven by allostery.
Atomistic model of a voltage-dependent ion channel in a biological membrane. Here, the membrane potential is modeled by an electric field.