A Comparison of Actin Filament Models by Molecular Dynamics Simulation

Abstract

Actin is a major structural protein of the eukaryotic cell, involved in cell motility and the structure of the cytoskeleton. While the cellular functions of actin are well understood, the atomistic structure of the actin filament (F-actin) is still unknown. Several models of F-actin have been proposed. Here, we introduce a new actin filament model based on X-ray fiber diffraction intensities and a previous filament model. Molecular dynamics (MD) simulations of a 13 subunit repeat of the filament were carried out for this new F-actin model, the Oda 2009 model and the Holmes 2004 model in order to investigate the conformational details of the actin filament and assess their quality in terms of structural integrity. Analysis of a number of structural determents such as the protomer dihedral angle, number of hydrogen bonds or the structural deviation among the 13 protomers suggest the Holmes 2004 model to be of lower quality than the other two models. The different strengths of our new filament model and Oda model may be bundled into an improved future F-actin model.In addition, simulations of the new filament model were carried out in the ADP and the ATP-bound states to study the differences in the hydrogen-bonding network of the nucleotide. Our simulations predict the significance of the residue Gln137 and shed light into the question why ATPase activity is only exhibited by the filamentous form of actin.