Residue-specific coarse-grained model of actin filaments

A challenge in understanding the molecular regulation of actin cytoskeleton is the development of computationally efficient and accurate models. We developed a coarse grained molecular dynamics model of actin filaments that incorporates residue-specific interactions through the C-alpha implicitsolvent model of Kim and Hummer (KH), modified to account for experimentally-determined actinactin interactions. While the KH model correctly predicts the broad features of actin-actin interactions, it does not consistently maintain all long- and short-pitch contacts required for a right handed helix of actin subunits. We show the latter can be achieved by specifying additional specific interactions between subdomains 3 and 4, two pairs between the D-loop and the cleft of subdomains 1 and 3, and one pair for short-pitch interaction. We also give the actin subunits flexibility to tilt/open to mimic the transition between G- and F- actin forms. The modified KH model is able to capture the critical contacts in actin filament formation and stabilization and should be useful to understand interactions of actin filaments to side binding proteins.