Thermodynamics and kinetics of actin filament nucleation

We have performed computer simulations and free energy calculations to dete rmine the thermodynamics and kinetics of actin nucleation and thus identify a probable nucleation pathway and critical nucleus size. The binding free energies of structures along the nucleation pathway are found through a com bination of electrostatic calculations and estimates of the entropic and su rface area contributions. The association kinetics for the formation of eac h structure are determined through a series of Brownian dynamics simulation s. The combination of the binding free energies and the association rate co nstants determines the dissociation rate constants, allowing for a complete characterization of the nucleation and polymerization kinetics. The result s indicate that the trimer is the size of the critical nucleus, and the rat e constants produce polymerization plots that agree very well with experime ntal results over a range of actin monomer concentrations.