Figure 5.

Possible schematic of the early stages of tP5abc collapse. (A) With no added salt, the A186U mutant exists in an extended (or unfolded) state (U) due to the large electrostatic excluded volume of its three helices. When rapidly mixed with ions, the molecule collapses to a compact intermediate state (I). The increase in ion concentration reduces the electrostatic excluded volume allowing the molecule to become more flexible. This change increases its conformational entropy and reduces its free energy, which all lead to faster collapse times. (B) The same arguments as in (A) apply to the wild type tP5abc, however, specific binding of Mg²⁺ ions reduces the enthalpy of the collapsed state, which can manifest as a faster collapse time as observed in the mixing experiments. Once specific binding has occurred, the wild type can proceed to fold to its native state, although this step is slow due to the large free energy barrier of secondary structure rearrangement.