Comparison of dynamic cross-correlation networks.

<p>Difference DCCM matrices (ΔDCCM) calculated between pairs of OM-bound and Apo simulations are mapped onto the initial structures of each OM-bound simulation. Edges connect residue pairs that have a positive (red) and a negative (green) ΔDCCM value, using a threshold of 0.16. Residues in the OM-binding site are represented as yellow spheres, while the CLD domain is coloured in blue.</p

Mapping of C^α RMSF profiles onto the cMotorD structure.

<p>RMSF values from Apo and OM-bound simulations are colour mapped onto the cMotorD structure from blue (0 Å) to red (3.4 Å). The average structure is used for each simulation. The thickness of the tube representation is proportional to the RMSF value. High flexibility regions and the OM binding site are also labelled.</p

Salt bridge clusters in wild type ApAAP.

<p>Salt bridges belonging to cluster 1 (A, blue), cluster 2 (B, E, cyan) and clusters 3 (B, yellow) and 4 (B, green) are shown as spheres and connected by sticks. C–D) Details on salt bridges belonging to cluster 1 and located in proximity of the catalytic site. E) Details of some salt bridge networks located in cluster 2. The α1-helix is highlighted as cyan cartoon. The sticks connecting the salt bridges are colored according to the persistence of the interactions in the simulations (from light to dark magenta for increasing persistence values).</p

Summary of the multi-replica all-atom MD simulations.

<p>Summary of the multi-replica all-atom MD simulations.</p

Collective motions in Apo and OM-bound simulations.

<p>A. Porcupine representation of PC1 (top panels) and PC2 (bottom) in ApoA1 (left panels) and OMA1 (right) simulations. The orange spikes show the direction and relative amplitude of motion of each residue along the PC. The approximate direction of the CLD hinge axis is also shown for Apo simulations (orange arrows). The two insets show the anti-correlated (Apo) and correlated (OM-bound) motions of the CLD (blue) and SH3 (green) subdomains. B. DynDom dynamic domain decomposition for ApoA1 PC1 (top) and the recovery stroke (bottom). The analysis was performed on the structures with minimum and maximum PC1 value from the MD simulation and on the experimental structures representing the pre-power stroke (PDB ID: 1QVI) and near-rigor (PDB ID: 1SR6) states for the recovery stroke. The fixed (white) and moving (yellow) domains identified by DynDom are shown, together with the hinge axis (orange) and the hinge regions (magenta).</p

Network of inter-residue contacts in the OM-binding site.

<p>Red edges connect pairs of residues that are found in contact for at least 70% of the simulation. All the residues within 8 Å from OM were included in the analysis. Contacts are reported for replica 1 only (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005826#pcbi.1005826.s014" target="_blank">S4 Fig</a> for all the replicas). For each chain, pairs that were consistently found in contact in both OM-bound simulations and in none of the Apo ones are labelled.</p

Correlated motions at the interdomain interface.

<p>A) The open structure of ApAAP identified by X-ray crystallography <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035686#pone.0035686-Harmat1" target="_blank">[33]</a> is shown as a reference. The observed crucial residues for mediating cross-correlated motions in the simulations of the ApAAP closed form (panel B) are shown as spheres. B) The dynamical cross-correlations at the interdomain interface (correlation threshold of 0.4) in wild type ApAAP are shown as red lines. The β-propeller and the catalytic domains are shown in pale-cyan (A)/blue (B) and pale-green (A)/white (B), respectively, whereas the α1-helix is highlighted in cyan. The hinge residue proposed for the opening of the catalytic cleft, D376 is shown in dark green (A) and black (B), respectively.</p

Protein dynamics fingerprint for wt, Δ21, and mutants ApAAP variants.

<p>The projections of the displacement described by the first principal component on the 3D structure are shown for wt (A), Δ21 (B), I12A (C), V13A (D), V16A (E), L19A (F), and I20A (G) ApAAP variants with the different simulation frames colored with different shade of colors from light cyan to purple. The catalytic triad and the α1-helix are shown as spheres and cartoon, respectively. The analyses were also carried out for the second and third components, which provide the same general view and are therefore not presented here.</p

Simulations of ApAAP in open conformation.

<p>A) The cross-correlated motions at the interdomain interface (correlation threshold of 0.4) in simulations of open ApAAP are shown as green lines (positive correlations) and blue lines (negative correlations). The β-propeller and the catalytic domains are shown in pale-green and white, respectively, whereas the α1-helix is highlighted in pale-cyan. D376, which is the hinge residue proposed for the opening of the catalytic cleft <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035686#pone.0035686-Harmat1" target="_blank">[33]</a> is shown. B) The salt bridge networks at the interface between the β-propeller and the catalytic domains in ApAAP open conformations are shown as spheres connected by yellow/green lines according to their persistence. The β-propeller domain and the catalytic domain are highlighted in pale-green and white, respectively, whereas the α1-helix in pale-cyan. Catalytic residues are shown as sticks.</p

Structure of the myosin motor domain and acto-myosin cycle.

<p>A. Cartoon representation of the motor domain structure (PDB ID: 4PA0 [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005826#pcbi.1005826.ref008" target="_blank">8</a>]), with the subdomains highlighted in different colours and OM shown as purple spheres. The motor domain is connected to the rest of myosin through the lever arm and the regulatory domain (not shown). B. Simplified representation of the acto-myosin cycle, where myosin switches between actin-bound (bottom) and -unbound (top) states and between up and down conformations of the lever arm.</p