Ligand-induced structural changes analysis of ribose-binding protein as studied by molecular dynamics simulations

Abstract

Background: The ribose-binding protein (RBP) from Escherichia coli is one of the representative structures of periplasmic binding proteins. Binding of ribose at the cleft between two domains causes a conformational change corresponding to a closure of two domains around the ligand. The RBP has been crystallized in the open and closed conformations.

Objective: With the complex trajectory as a control, our goal was to study the conformation changes induced by the detachment of the ligand, and the results have been revealed from two computational tools, MD simulations and elastic network models.

Methods: Molecular dynamics (MD) simulations were performed to study the conformation changes of RBP starting from the open-apo, closed-holo and closed-apo conformations.

Results: The evolution of the domain opening angle θ clearly indicates large structural changes. The simulations indicate that the closed states in the absence of ribose are inclined to transition to the open states and that ribose-free RBP exists in a wide range of conformations. The first three dominant principal motions derived from the closed-apo trajectories, consisting of rotating, bending and twisting motions, account for the major rearrangement of the domains from the closed to the open conformation.

Conclusions: The motions showed a strong one-to-one correspondence with the slowest modes from our previous study of RBP with the anisotropic network model (ANM). The results obtained for RBP contribute to the generalization of robustness for protein domain motion studies using either the ANM or PCA for trajectories obtained from MD.

Keywords: Ribose-binding protein; conformational change; elastic network model; molecular dynamics simulation.

Figure 1.

(a) The X-ray crystal structure of RBP in the open-apo state (PDB code: 1URP) and (b) the closed-holostate (PDB code: 2DRI). Ribose is marked in stick representation and coloured in yellow. The C-domain of RBP is marked in red, the N-domain of RBP is marked in blue, and the hinge segments is marked in green.

Figure 2.

Distribution of domain opening $\theta$ corresponding to the three simulations.

Figure 3.

RMSD of the Ca atoms from the crystal structures for the three systems as a function of time.

Figure 4.

Structural stability of each domain individually: the RMSD of the Ca atoms from the starting structure of the N-terminal domain (a) and C-terminal domain (b).

Figure 5.

Root mean square fluctuation (RMSF) profile of the Ca atoms obtained from the three simulations.

Figure 6.

Hbonds were formed between ribose and residues of RBP in the closed-ligand simulation. Hbonds are represented as broken lines.

Figure 7.

The three interdomain H-bonds (O$\delta$Ser68-N Ser136, N Ser68-O Gly134 and NGln91-O$\gamma$Ser136) were formed in the closed structure of ribose-binding. Hbonds are represented as broken lines.

Figure 8.

The hydrophobic contact distances between the four residues and ribose all remain constant in the closed-ligand simulation.

Figure 9.

The snapshots are taken from the closed-ligand simulation (left) and closed-apo simulation (right) at 30 ns.

Figure 10.

Projections of all three simulations of the apo-transition trajectory onto the first two eigenvectors.

Figure 11.

The movements along the first three eigenvectors for the closed-apo simulations (a) and the slowest modes of RBP by ANM (b).