Actin is central to the function of the cell and plays many important roles. Structural biology has provided us with a wealth of actin and actin-related protein structures in recent years, and using these structures along with a wide array of computational techniques we are able to look at the dynamics and interactions of actin at the molecular level. Our current work includes many different projects looking at the interaction and regulation of actin and actin-associated proteins. A few of these projects are summarized below.
- Arp2/3 Complex
We have been performing large-scale molecular dynamics simulations of the inactive complex to try and understand the activation mechanism. We have also been working with Matt Welch (UC Berkeley) to understand the branch structure on the mother filament.
- Capping Protein
We have been collaborating with John Cooper’s lab (Washington University) to understand the interaction with CP and the barbed end and how this interaction is regulated by CARMIL, PIP2, and myotrophin.
We are performing molecular docking and molecular dynamics studies to determine the basis of interaction between cofilin and the filament to hopefully gain insight into the mechanism of filament severing.
- Multi-scale Modeling
We have performed long time-scale molecular dynamics trajectories of short actin filaments and have used these simulations to parameterize coarse-grained models of actin filaments.
- F-Actin Binding Drugs
We have been studying the binding of phalloidin and jasplakinolide, and how these compounds stabilize the actin filament.
- Bacterial Rho Mimics
We are studying how mimics of Rho GTPases from Shigella function within a host cell.