The actin cytoskeleton a complex polymer network that gives cells structure and allows them to move and to divide. This network is constantly turning over, with the polymers assembling and disassembling on the time scale of seconds to minutes. In order to control with spatial and temporal resolution the amount of actin polymer, cells use other proteins to nucleate formation of new polymers, including the Arp2/3 complex, which forms branched actin networks, and ENA/VASP, which is involved in the formations of cell protrusions known as filopodia.<br/> <br/>Actin monomers are large globular proteins with four major domains. Monomers adopt a twisted conformation in solution, and a flat, planar conformation when in a filament. In this work, we will show how the conformational free energy landscape in terms of this macromolecular twist angle can be sampled using metadynamics simulations, and discuss our recent methodological advancements that make this computation tractable. We will then show how the conformational landscape changes when the protein is in a filament, and how this landscape changes when actin is associated with helical peptides known as WH2 domains, involved in nucleation processes such as by Arp2/3 and ENA/VASP. Finally, we will discuss how these molecular level changes might influence the thermodynamics and kinetics of filament assembly.

Conformational landscape of actin monomers and its implications for filament assembly

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.