ON THE TIME-SCALE AND TIME-COURSE OF PROTEIN CONFORMATIONAL-CHANGES

Proteins change their global conformation very slowly compared to the time scales of most localized internal motion. The relationship between these slow and fast processes was investigated with the aid of a stochastic model recently applied to a related problem of protein folding [Zwanzig et al., Proc. Natl. Acad. Sci. 89, 20 (1992)]. In the present study a change in conformation was treated as a bond rotational isomerization that may only occur when several other gating bonds simultaneously assume permissive orientations. The requirement of correct orientation of these gating bonds is analogous to the alignment of the tumblers in a lock. For a range of reasonable choices of parameters, this model generated realistic time scales for protein conformational changes. Although the transition time depended on the value of an energy bias against the permissive position of a gating bond, the model could still generate reasonable transition times in the absence of an energy bias. For a wide range of parameters chosen to give typical experimental rates for biological transitions, the model predicted conformational changes with simple exponential kinetics.