l - People

The motion of GlnBP (see Chapter 4, supplementary discussion, for biological function)
as it binds glutamine involves large-displacement domain hinge bending, experimentally
determined to take ~5ns.[105] 6 ns Molecular Dynamics simulations of the apo structure
failed to result in domain closure, possibly in part because closing time should be a
stochastic process and in part because the ligand may induce closure, while the dynamics
of the apo structure were computed with no ligand present.[105] In this section we show
that the Conformation Explorer can predict the ligand-bound conformation of this protein
based on no prior knowledge beyond the set of coordinates of the apo structure and its
ligand. The apo or starting structure used[106], and the holo structure[107] both originate
in E. coli.
As mentioned earlier, the first step of the process is the prediction of the hinge location.
For GlnBP FlexOracle[90] found a hinge at residues 86-89 and 182-185. We selected
residues 88,89,181, and 182 as the hinge location (Figure 4) for the purpose of generating
the rotations, but since the flexure occurs at the boundary between L and M, this
adjustment makes little difference. We then generated conformations as described in the
Methods.
Figure 5.3.a shows each of the conformers (represented as spheres), positioned according
the angular orientation of Domain 3, and colored by sRMSD. The conformer with lowest
sRMSD is shown with a larger radius than the others. The starting structure is indicated
with the blue arrow, and displayed in inset 5.3.b. It should not be surprising that this is
also the structure with lowest domain distortion, since domain distortion is measured
254