The Free Energy Profile of Tubulin Straight-Bent Conformational Changes, with Implications for Microtubule Assembly and Drug Discovery
Figure 5
The (a) probability distribution and (b) free energy profile for the colchicine-bound tubulin as a function of intradimer rotation.
Intradimer rotation of the endpoint structures, the “straight” taxol-liganded, zinc-stabilized protofilament tubulin and “bent” α1β1 heterodimer from the T2R-colchicine complex, are denoted at θ∼0° (blue dash) and θ∼12° (red dash), respectively. Intradimer rotations observed in crystal structures of colchicine-bound tubulins are denoted as dotted lines at θ∼7.8° (both α1β1 and α2β2 heterodimers of T2R-colchicine-ustiloxin complex). Individual probability histograms corresponding to each umbrella window is shown in Figure S2b in Text S1.