Fig. 4.
Kinetics of the transition from nonspecific to specific DNA binding. (A) Illustration of a sliding–binding simulation for the recognition helix of MAD from the MAD-MAX heterodimer. The searching protein, shown in lucid blue, is initially positioned near the edge of the 100-bp dsDNA and starts sliding along the helical DNA path on nonspecific segments (I). It then locates the binding site, but the specific protein–DNA interface is not yet formed (II). The time required from the start of the search until the protein locates its binding site, τ1, is then recorded. The protein can then either switch from the trapped state to form high affinity interactions with the target site (IV) or continue to diffuse to other regions of the DNA (III) until it again locates the target and eventually fully binds to it (IV). The time elapsed from the start of the search until formation of the specific interface, τ2, is then recorded. Trajectories of three variant peptides with different χprot are shown: (A) wild-type peptide (χprot = 0.1), (B) peptide 33 (χprot = 0.4), and (C) peptide 19 (χprot = 0.6) (see Fig. S1). Each trajectory is analyzed in terms of the location of the protein along the DNA (blue) and the fraction of specific contacts formed at the binding site (gray). The times τ1 and τ2 are indicated by red dashed lines. The correlations between τ1 and τ2 from 100 simulations of each peptide system are shown and indicate greater correlation as χprot increases.