Computer simulations of actin polymerization can explain the barbed-pointed end asymmetry

Computer simulations of actin polymerization were performed to investigate the role of electrostatic interactions in determining polymerization rates. Atomically detailed models of actin monomers and filaments were used in co njunction with a Brownian dynamics method. The simulations were able to rep roduce the measured barbed end association rates over a range of ionic stre ngths and predicted a slower growing pointed end, in agreement with experim ent. Similar simulations neglecting electrostatic interactions indicate tha t configurational and entropic factors may actually favor polymerization at the pointed end, but electrostatic interactions remove this trend. This re sult would indicate that polymerization at the pointed end is not only limi ted by diffusion, but faces electrostatic forces that oppose binding. The b inding of the actin depolymerizing factor (ADF) and G-actin complex to the end of a filament was also simulated. In this case, electrostatic steering effects lead to an increase in the simulated association rate. Together, th e results indicate that simulations provide a realistic description of both polymerization and the binding of more complex structures to actin filamen ts. (C) 1999 Academic Press.