FIG. 5.

Time series and probability distributions for θ_B, the degree of freedom which describes in-plane rotation of the aromatic ring in the binding site, for simulations with the weakest restraints. (a) shows a 1 ns simulation restraining to orientation 1 [Fig. 4(a)], (b) shows a 1 ns simulation restraining to orientation 2 [Fig. 4(b)], and (c) shows a 5 ns simulation restraining to orientation 2. In order for estimates computed by simulations restraining to the two orientations to be converged, both simulations must sample the same regions of phase space, but it is apparent from (a) and (b) that they have not done so on 1 ns time scales, since the distribution shown in (b) includes a region of phase space never sampled in (a). Here, in (c), it is obvious that phenol spends time in at least three different orientations. Shown here are the simulations with the weakest restraints, where the restraints were sufficiently small that the distribution of angles sampled was essentially the same as in the unrestrained case.