Fluctuations of Phe43 cavity residues.

<p>(<b>A</b>) Identification of residues that line the Phe43 cavity in HIV gp120. The point of view is as in Fig. 1A, but rotated clockwise about the page normal by approximately 40°. (<b>B</b>) RMS residue fluctuations of Phe43-cavity lining residues as driven by the linear combination of the 10 slowest modes from full atomic normal mode analysis. Values are shown in bars for the identified residues from isolated gp120 (light blue) and for gp120 complexed with CD4 D1 (burgundy), F23 (pale yellow) and CD4M33 (pale turquoise). Residues are placed in neighboring order, starting from W112 at upper left and moving roughly clockwise as viewed in Fig. 7A.</p

Hinge sites of gp120 based on gp120 ternary complex ENM calculation.

<p>Hinge sites of gp120 based on gp120 ternary complex ENM calculation.</p

The gp120 transition pathway between CD4- and F105-bound states.

<p>(<b>A)</b> Monitor cues as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052170#pone-0052170-g011" target="_blank">Figure 11<b>A</b></a>. (<b>B</b>) The progression of monitor distances, colored as in <b>A</b>, during the gp120 trajectory. Numbers below the x-axis mark the positions of structures visualized in panel <b>C</b>. (<b>C</b>) The identified gp120 transition intermediates along the trajectory starting from the CD4-bound state (1) and ending at the F105-bound state (8). Structures are drawn as Cα backbones colored spectrally from N (blue) to C (red).</p

Conformational plasticity of gp120:D1.

<p>Features from the four slowest modes analyzed and displayed as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052170#pone-0052170-g003" target="_blank">Figure 3</a>, but for gp120 in its complex with CD4 D1. (<b>A</b>) Fluctuations mapped onto worm diagrams. (<b>B</b>) Superposition of conformers generated at extremes of the fluctuations. (<b>C</b>) Alpha-carbon RMSF plots.</p

The solvent shell for molecular dynamic simulation of HIV gp120.

<p>The isolated gp120 molecule is shown as a backbone worm and the 1150 TIP3P water molecules are shown as oxygen ball (red) and O-H bond sticks (white).</p

Conformational equilibria between CD4-, F105- and b12-bound conformations of gp120.

<p>Conformational equilibria between CD4-, F105- and b12-bound conformations of gp120.</p

Conformational plasticity of isolated gp120.

<p>Features are shown for the four slowest modes from a full atomic normal mode analysis in a solvent shell. (<b>A</b>) Fluctuations from frequency-weighted slow modes are mapped onto worm diagrams depicting the course of the polypeptide backbone of HIV gp120. The thickness of each worm is proportional to the amplitude of the calculated fluctuations. (<b>B</b>) Superposition of conformers (red and green) generated at extremes of the fluctuations (The relative amplitude of fluctuations define the limits of the excursions on gp120; see Methods). (<b>C</b>) Alpha-carbon root-mean-square fluctuation (RMSF) plots.</p

The RMSD between minimized and crystal structures of gp120.

<p>The RMSD between minimized and crystal structures of gp120.</p

Collective motions in gp120 as computed by the ENM.

<p>(<b>A</b>) Comparison of experimental and ‘theoretical’ B-factors (mean-square fluctuations) for the structure of core HIV-1 gp120:CD4(D1D2):Fab17b. Experimental B-factors are from the crystal structure (PDB ID: 1G9N) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052170#pone.0052170-Kwong2" target="_blank">[10]</a>; theoretical values derive from the mean-squared fluctuations, <|<b>r</b> – <b>r₀</b>|²>, as summed from all modes from an isotropic ENM calculation from the entire gp120:D1:V_HV_L complex, noting that B = 8π²<|<b>r</b> – <b>r₀</b>|²>/3. Thus, the ENM profile has been uniformly scaled to match the experimental data. The correlation coefficient between the two profiles, which is scale invariant, is 0.77. (<b>B</b>) Mean-square (ms) fluctuations represented by the frequency weighted sum of the 10 slowest modes. Analyses are from gp120 as isolated from the gp120:CD4∶17b complex and in various complexes as indicated in the color key. Arrows below the sequence place the hinge sites as determined from the analysis of gp120 in complex with the D1 domain of CD4 and the V_HV_L domains of antibody 17b. (<b>C</b>) The hinge sites (red spheres) mapped onto a ribbon drawing of the gp120 structure (grey). (<b>D</b>) Ribbon diagrams of the gp120 structure color-coded spectrally according to residue fluctuations. Red corresponds to the highest amplitudes and blue to the lowest amplitudes.</p

Cross correlations of fluctuations of conserved residues lining the Phe43 cavity.

<p>The cross correlation values are based on the sum of the 10 slowest modes. (<b>A</b>) gp120. (<b>B</b>) gp120:CD4(D1). (<b>C</b>) gp120:F23. (<b>D</b>) gp120:CD4M33. Specific residues are identified in the same order as in Fig. 7B.</p