Mutual information of residue pairs in calmodulin.

<p>The mutual information, , associated with side-chain fluctuations of residue pairs in calmodulin. Plots (b)–(f) display the mutual information signal∶noise ratio, (upper left triangles) and the excess mutual information (lower right triangles), as indicated in (a). The - and -axes run over labels, and respectively, of residues in the amino acid sequence, excluding those lacking rotameric freedom in our model. Scale bars for the signal∶noise ratio and the excess mutual information are presented on the top and bottom left, respectively. Results are shown for the following combinations of interactions: (b) repulsive sterics (S), (c) implicit solvent (IS) (d) Lennard-Jones (LJ) interaction comprising repulsive sterics and van der Waals attractions, (e) hydrogen bonding and salt-bridges (HBSB), and (f) the full potential (LJ+HBSB+IS). Residue 30K, which we scrutinize in detail later (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi-1002168-g005" target="_blank">Fig. 5</a>), is highlighted in (f) for reference.</p

Structural representations of extended crystalline calmodulin.

<p>The crystal structure (a) and contact map (b) of calcium-bound calmodulin (3cln <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi.1002168-Babu1" target="_blank">[39]</a>). The calcium ions are shown in yellow, and several residues are labeled in both panels for reference. The distance between each pair of atoms is indicated by color (see scale bar) in (b), where - and -axes run over residue labels. The residue labeling corresponds to the full sequence, however residues that do not possess torsional degrees of freedom in our model (A, G, P, and all residues bound to the calcium ions) are excluded from the contact map.</p

Distance dependence of mutual information in different NMR models of barstar.

<p>The average excess mutual information per residue pair is plotted here for various atomic interactions, binned according to the - inter-residue distance, for the crystal structure (1a19 <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi.1002168-Ratnaparkhi1" target="_blank">[47]</a>) and four NMR model structures (1btb <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi.1002168-Lubienski1" target="_blank">[43]</a>) of barstar, using the full LJ+IS+HBSB potential. See <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#s4" target="_blank">Methods</a> for details.</p

Single-residue perturbations in barstar.

<p>Changes in the Gibbs entropy of each residue in barstar (1a19 <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi.1002168-Ratnaparkhi1" target="_blank">[47]</a>) that resulted from perturbations to single side-chains. Residues whose entropy changes by a significant amount, according to Student's t-test at the 90% level, are shown in color. Red indicates increased entropy, blue indicates decreased entropy (see scale bar). Although side-chains are depicted in their crystallographic arrangements for graphical simplicity, note that is a measure of the extent of fluctuations among a wide variety of distinct packings. For the results presented in panel (a), I86 (shown in black and circled) was mutated to G. For those of panel (b) E46 (shown in black and circled) was constrained to its crystallographic configuration.</p

Mutual information by residue type.

<p>The average excess mutual information per interaction, , for all twenty amino acids. In each case data was pooled from all applicable pairs of fluctuating residues within a set of twelve small globular proteins (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#s4" target="_blank">Methods</a>).</p

Correlation between residue 30 and other residues in calmodulin.

<p>The extent of correlation between residue 30 (shown in black and circled) and all other side-chains in calmodulin (3cln <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi.1002168-Babu1" target="_blank">[39]</a>) is shown here. In (a) each residue is colored according to the magnitude of its excess mutual information with 30K (see left scale bar and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#pcbi-1002168-g003" target="_blank">Fig. 3</a>). Coloring in (b) indicates the change in each residue's side chain entropy effected by the mutation K30G. Here, red represents increased entropy and blue decreased entropy (see right scale bar). See <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002168#s4" target="_blank">Methods</a> for details.</p