Actin is a protein which forms long filaments in cells. For example, it comprises the thin filament of muscle cells, and is one of the main proteins found in the cytoskeleton. Individual actin monomers adopt at least two major conformations, referred to as G-actin (non-filamentous) and F-actin (filamentous). It is known that the actin nucleotide state of the individual subunits can influence properties of the filament, such as the persistence length and torsional rigidity (Fan, et al., Biophys J 2012). Previous work has also demonstrated that the nucleotide state can influence the conformation of the DB-loop in subdomain 2 of actin (Pfaendtner, et al., PNAS 2009). Furthermore, the DB-loop can help to regulate filament stiffness, related to its interaction with the cleft between subdomains 1 and 3 of an adjacent actin monomer. Recently, it has been demonstrated that specific binding sites for cations in the DB-loop have a large influence on the persistence length of actin filaments (Kang, et al., PNAS 2012). We have carried out all-atom molecular dynamics (MD) simulations of long actin filaments (26-mer periodic filaments), starting from two different recently published F-actin conformations, in the presence of the specific magnesium cations. The MD simulations provide atomistic insight into the influence of the specific cations on DB-loop dynamics in the filament environment. Additionally, we characterize actin filament properties in the presence of these ions. Finally, coarse-grained (CG) analysis of the filaments allows us to study the influence of the ions on interactions between actin CG domains, and how those interactions are changed compared to the filament without specific ions present. This will help to guide future CG models of the filament in which multiple states (for example, the presence or absence of an ion in the DB-loop CG site) are incorporated.

Actin DB-loop and filament dynamics in the presence of specific magnesium cations

246th National Meeting (2013)

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