Exploring global motions and correlations in the ribosome

Abstract

We studied slower global coupled motions of the ribosome with half a microsecond of coarse-grained molecular dynamics. A low-resolution anharmonic network model that allows for the evolution of tertiary structure and long-scale sampling was developed and parameterized. Most importantly, we find that functionally important movements of L7/L12 and L1 lateral stalks are anticorrelated. Other principal directions of motions include widening of the tRNA cleft and the rotation of the small subunit which occurs as one block and is in phase with the movement of L1 stalk. The effect of the dynamical correlation pattern on the elongation process is discussed. Small fluctuations of the 3' tRNA termini and anticodon nucleotides show tight alignment of substrates for the reaction. Our model provides an efficient and reliable way to study the dynamics of large biomolecular systems composed of both proteins and nucleic acids.

FIGURE 1

Plot shows the g(r) distribution for the P–P pairs in the 70S ribosome structure (black solid line). The corresponding (r) is shown as a black dotted line. The structural interactions for g(r) were extracted: the first neighbor and paired-bases distributions are shown in magenta, whereas the interactions between second and third neighbors along the chain (corresponding to angle and dihedral interactions) are shown as cyan solid lines and the Morse potential as cyan dashed lines. The nonbonded interactions, after subtracting the structural interactions, are shown as a green solid line with a corresponding Boltzmann inversion shown as a green dotted line. The green long-dashed line shows the fitted Morse potential. The potential used outside the cutoff is shown as green dashed line. The inset shows the radial distribution and the respective potential for the paired bases in the secondary structure. The normalization of g(r) and the additive constant for the potential energy are arbitrary.

FIGURE 2

Plot shows the g(r) distribution for the Cα–Cα pairs in the 70S ribosome structure (black solid line). The corresponding (r) is shown as a black dotted line. For g(r) the structural interactions were extracted (cyan solid lines) with the corresponding fitted Morse potentials (cyan dashed lines). The nonbonded interactions, after subtracting the structural interactions, are shown as a green solid line. Green dashed line shows the fitted Morse potential outside the cutoff. The inset shows the g(r) distribution for subsequent amino acids, the Boltzmann inversion and the corresponding fitted harmonic potential. The normalization of g(r) and the additive constant of the potential energy are arbitrary.

FIGURE 3

Ribosome structure colored according to the average temperature factors derived from a 500-ns molecular dynamics simulation. The scale is from red, which shows the highest fluctuations, through white to blue showing the smallest movements. The inset shows the relative position of the small subunit (yellow) with respect to the large subunit (cyan).

FIGURE 4

Root mean-square fluctuations of ribosomal fragments. Single peaks correspond to termini.

FIGURE 5

Principal directions of movements for the L7/L12 and L1 stalks. Green arrows show the anticorrelated direction of movement (see Supplementary Movie in Supplementary Material). (Colors: 30S in yellow; 50S in cyan; tRNA in green; and S7 and S11 in white. The axis of rotation of L1 is shown in gray.) The symbols ⊙ and ⊗ show the movement out of and into the plane of the figure, respectively.

FIGURE 6

Dynamical correlation pattern showing the anticorrelated movement of L1 and L7/L12 stalks (see also Supplementary Movie in Supplementary Material). (Correlation scale and coloring: −1 < r < −0.7 = blue; −0.7 < r < −0.1 = cyan; 0.1 < r < 0.7 = yellow; and 0.7 < r < 1.0 = red.)

FIGURE 7

Power spectrum for two principal modes representing the rotation of ribosomal subunits and the anticorrelated movement of L1 and L7/L12 stalks derived from a sample 200-ns MD simulation.

FIGURE 8

Root mean-square fluctuations of the A- and P-site tRNAs and mRNA chain derived from a sample 200-ns MD simulation. Anticodon and CCA-3′ termini are annotated.