Ion channel & transporter function
Ion channels and transporter proteins allow cells to move biologically important ions and molecules across their various membranes in order to regulate their internal composition and metabolism. We seek to understand how these crucial protein machines work on many levels, from the tiny molecular details of how they interact with their substrates up to bulk transport properties at the scale of organelles and cells. To do this we use a variety of techniques including molecular dynamics simulations, continuum calculations, and kinetic modelling.
Membrane mechanics
We study the structure and properties of cellular membranes and their interactions with proteins at several scales. We identify small-scale and individualized interactions using all-atom MD, such as characterizing the activity of lipid scramblases in response to different membrane environments and locating lipid binding sites on ion channels that modulate channel activity. We study large membrane deformations by membrane-remodeling protein complexes, such as constriction of a flat bilayer for vesicle budding, using coarse-grained simulations. At the largest scale, our group develops continuum models of membranes that characterize how insertion of a transmembrane protein induces changes to membrane structure and mechanical properties.
Small molecule interactions
Many small molecules - either medicines and biological tools or naturally occurring metabolites and lipids - work by interacting with specific binding sites on their protein targets in ways that modify protein function. Many projects in the lab explore these types of interactions, particularly in the context of how drug-like molecules and naturally occurring lipids regulate membrane proteins. We use approaches that include different types of molecular simulations, including coarse-grained simulations, and high-resolution rigid or flexible molecular docking, often combining static and dynamic techniques to gain greater insights.