xcexb1xcexb2-tubulin dimers need to convert between a bent conformation observed for free dimers in solution and a straight conformation required for incorporation into the microtubule lattice. Here, we investigate the free energy landscape of xcexb1xcexb2-tubulin using molecular dynamics simulations, emphasizing implications for models of assembly, and modulation of the conformational landscape by colchicine, a tubulin-binding drug that inhibits microtubule polymerization. Specifically, we performed molecular dynamics, potential-of-mean force simulations to obtain the free energy profile for unpolymerized GDP-bound tubulin as a function of the xe2x88xbc12xc2xb0 intradimer rotation differentiating the straight and bent conformers. Our results predict that the unassembled GDP-tubulin heterodimer exists in a continuum of conformations ranging between straight and bent, but, in agreement with existing structural data, suggests that an intermediate bent state has a lower free energy (by xe2x88xbc1 kcal/mol) and thus dominates in solution. In agreement with predictions of the lattice model of microtubule assembly, lateral binding of two xcexb1xcexb2-tubulins strongly shifts the conformational equilibrium towards the straight state, which is then xe2x88xbc1 kcal/mol lower in free energy than the bent state. Finally, calculations of colchicine binding to a single xcexb1xcexb2-tubulin dimer strongly shifts the equilibrium toward the bent states, and disfavors the straight state to the extent that it is no longer thermodynamically populated. 