Chemical Functioning of Actin Filament Nucleation

Characterization of Actin Nucleation Pathway Through Computer Simulations

Abstract

We have performed computer simulationsand free energy calculations to determine the thermodynamics and kinetics ofactin nucleation and thus identify a probable nucleation pathway and criticalnucleus size. The binding free energies of structures along the nucleationpathway are found through a combination of electrostatic calculations andestimates of the entropic and surface area contributions. The associationkinetics for the formation of each structure are determined through a series ofBrownian dynamics simulations. The combination of the binding free energies andthe association rate constants determines the dissociation rate constants,allowing for a complete characterization of the nucleation and polymerizationkinetics. The results indicate that the trimer is the size of the criticalnucleus, and the rate constants produce polymerization plots that agree verywell with experimental results over a range of actin monomer concentrations.