Citrate synthase plays a fundamental role in the metabolic cycle of the cell. Its catalytic mechanism is complex involving the binding of two substrates that cause a domain movement. In this paper, we used classical molecular dynamics simulations and umbrella-sampling simulations to determine the potential of mean force along a reaction coordinate for the domain movement in ligand-free citrate synthase from pig (Sus scrofa). The results show that, at 293 K, the closed-domain conformation has a similar to 4 k(b)T higher energy than the open-domain conformation. In a simple two-state model, this difference means that the enzyme spends 98% of the time in the open-domain conformation ready to receive the substrate, oxaloacetate, rather than the closed-domain conformation where the binding site would be inaccessible to the substrate. Given that experimental evidence indicates that the binding of oxaloacetate induces at least partial closure, this would imply an induced-fit mechanism which we argue is applicable to all enzymes with a functional domain movement for reasons of catalytic efficiency. A barrier of 4 k(b)T gives an estimation of the mean first passage time in the range 1-10 mu s.