A model is presented for relating the binding of the inactivation N-terminal to the ion pore of the Shaker potassium channel (ShB) to the bimolecular binding of the N-terminal peptide with the deletion mutant ShBDelta6-46. The binding site is modeled as a small patch on the surface of the channel protein, to which the N-terminal "inactivation ball" is tethered by a flexible linker. The potential energy due to electrostatic interactions between the channel and the N-terminal is betaU(r) = -Qexp[-(r - a)/lambda]/(1 + a/lambda)r, where a is the closest approach distance and A is the screening length determined by the ionic strength. The probability density for the end-to-end vector of the flexible linker (with L residues) is taken from a previous study [Zhou, J. Phys. Chem. B 2001, 105, 6763] as p(r) = (3/4pil(p)bL)(3/2)exp(-3r(2)/4l(p)bL)(1-5l(p)/4bL +...). The intramolecular binding rate constant k(on)(in) of the intact ShB is related to the bimolecular binding rate constant k(on)(bi) via k(on)(in) = k(on)(bi)p(a)/integralexp[-betaU(r)]p(r)dV. The model rationalizes a number of important experimental observations. (1) The weaker ionic strength dependence of k(on)(in) is quantitatively reproduced by the relation between k(on)(in) and k(on)(bi). (2) The linker length dependence of k(on)(in) (observed when the linker length is reduced by deletion and extended by insertion) is qualitatively predicted by the L dependence of p(r). (3) The fact that k(off)(in) = k(off)(bi) and both are insensitive to the change in ionic strength is due to the stereospecificity of the binding site. If the binding of the activation N-terminal were to occur in a bimolecular fashion, the millisecond inactivation time would have required the presence of the N-terminal at a concentration of 0.2 mM, even after considering the binding rate enhancement by the electrostatic attraction of the channel pore. The difficult task of maintaining such a high concentration underscores the importance of covalently linking the inactivation peptide to the ion channel.