Three-dimensional structures of the proteins studied in this work. The initial structure is placed in the center, and the targets are oriented in such a way that their C-terminal domains are best fitted. N-terminal domain is in green, C-terminal domain is in cyan, and the linker is in magenta. The Ca2+ ions are shown as gray spheres, the bound ligand molecules are shown in gray surface representations.
(a) Schematic representations of the defined bending angles θ, θ N, θ C, and the torsional angle φ. (b) θ/φ plot for the various target structures (filled circles) and the initial structure (empty circle). Histograms of the θ/φ pairs calculated from the 120 ns MD simulation (a total of 60 000 conformations) is overlaid as a contour map. The initial structure resides in the most visited region of the conformational space during the simulation. Only the target structure 1rfj is visited within this time window.
(a) Best PRS prediction of the displacement vectors (green) belonging to the 3cln to 1lin conformational change, overlaid on the initial structure. The main motion is a bending of the two lobes accompanied by rotation of the linker, where motions are especially accentuated in the region of residues 75–90. (b) Coordination of the E31 related Ca2+ ion. The side-chain (χ 1,χ 2) angles of E31 are in (t,t) conformation. Two alternate conformations of E31 which do not clash with any other heavy atoms in this conformation are also shown as transparent traces. These have (t,g − ) and (g −,g +) conformations for the (χ 1,χ 2) angle pair. The thick red arrow represents the best perturbation direction of E31 in both figures.
Degree of ionization as a function of pH for (a) Asp/Glu (36 residues) and (b) Lys/Arg (13 residues) amino acid types. E31 (dashed) and D122 (gray) are distinguished as those capable of changing ionization with subtle pH variations at physiological conditions. The standard pK a values for non-perturbed residues (Ref. 83) are 4.4 for Asp/Glu, 10.0 for Lys, and 12.0 for Arg.
Target calmodulin structures studied in this work.
RMSD between pairs of structures listed in Table I. Lower diagonal: RMSD between overall structures; upper diagonal: RMSD between N-lobe (bold) and C-lobe (italic) domains only. Overlap between the experimental displacement vectors ΔS are also displayed in parentheses.
Best overlap values obtained for proteins studied by PRS and modal analysis.a
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