36 research outputs found
Comparison of simulations from different models of complex Efb-C:C3d.
<p><b>(A)</b> RMSD (Cα) from the respective initial structure for the highest ranking RosettaDock models of complex Efb-C:C3d as a function of simulation time; simulations were performed at 303 K; highlighted in black is the simulation starting from the experimental structure, and in blue and orange from two selected models (also shown in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006182#pcbi.1006182.g006" target="_blank">Fig 6</a>); in grey are shown all simulations starting from the 20 highest scoring models. <b>(B)</b> RMSD after 40 ns simulation plotted versus the RMSD deviation of the model from the crystal structure; simulations started from the RosettaDock models at two different temperatures; at the higher temperature (300 and 340K).</p
Model r37 (blue) and r44 (orange) of G3:HER2_IV show similarity at the C-terminal region.
<p><b>(A)</b> Model overview <b>(B)</b> Hydrophobic interactions between F112 and a patch formed by F555 and V563 are conserved in both models. This works as an anchor that allows a pivoting to the correct pose. <b>(C)</b> The movement (indicated with an arrow) is facilitated by the additional hydrophobic contacts from I79 and F81 that slide around F555.</p
Root-mean-square deviation from the position of Cα atoms in the respective models of G3:HER2_IV complex as a function of simulation time.
<p>While some models rapidly move away from the initial pose, others only deviate from the initial structure when temperature is increased. The only model that even after 20 ns simulation at a temperature of 390 K remains close to the initial structure is model r37, that is, the one closest to the correct structure.</p
RMSD (for Cα atoms) from the reference experimental structure as a function of time along simulations at 303 K for the G3:HER2_IV complex.
<p>Simulations starting from model r37 or from the experimental structure explore a narrow range of conformations close to the experimental structure. The simulation starting from model r44 converges to the correct structure after about 50 ns, suggesting that, despite the remarkable structural difference from the correct structure, model r44 is within the native basin of the free energy surface. All the other trajectories do not lead to the correct state after 32 ns simulation. A simulation started from the experimental structure is also shown: the RMSD fluctuates around 1 Å indicating high rigidity of the complex.</p
RMSD from the reference experimental structure as a function of time along simulations at 303 K for the models of Efb-C:C3d complex.
<p>Model r1 (blue) is close to the experimental structure and stays stable throughout the simulation. The trajectory starting from model r18 (orange) converges to the correct structure after about 30 ns.</p
Cartoon representation of the crystallographic and NMR structures.
<p>(A) Crystallographic structure from PDB file 1G8I; (B) NMR structure, the first model that appears in the PDB file 2LCP. Residues 11–174 between H1 and H9 define the protein core (PC). The definitions of the other protein segments are given in the section “Material and Method” and in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074383#pone-0074383-t001" target="_blank">Table 1</a>.</p
RMSDs of the protein core evaluated with respect to the crystal structure along the MD trajectories.
<p>Gray line: RMSD evaluated along the 250 ns of the MD-XR trajectory. Orange: RMSD evaluated along the 525 ns of the MD-NMR simulation. Smoothed RMSDs signals are reported as black lines.</p
Apparent pseudo first-order rate constants for DSE involving each chaperone/subunit–Nte pair 1000×h<sup>−1</sup> experimentally measured [11].
<p>Apparent pseudo first-order rate constants for DSE involving each chaperone/subunit–Nte pair 1000×h<sup>−1</sup> experimentally measured <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063065#pone.0063065-Rose2" target="_blank">[11]</a>.</p
Modulation of a Protein Free-Energy Landscape by Circular Permutation
Circular
permutations usually retain the native structure and function
of a protein while inevitably perturbing its folding dynamics. By
using simulations with a structure-based model and a rigorous methodology
to determine free-energy surfaces from trajectories, we evaluate the
effect of a circular permutation on the free-energy landscape of the
protein T4 lysozyme. We observe changes which, although subtle, largely
affect the cooperativity between the two subdomains. Such a change
in cooperativity has been previously experimentally observed and recently
also characterized using single molecule optical tweezers and the
Crooks relation. The free-energy landscapes show that both the wild
type and circular permutant have an on-pathway intermediate, previously
experimentally characterized, in which one of the subdomains is completely
formed. The landscapes, however, differ in the position of the rate-limiting
step for folding, which occurs before the intermediate in the wild
type and after in the circular permutant. This shift of transition
state explains the observed change in the cooperativity. The underlying
free-energy landscape thus provides a microscopic description of the
folding dynamics and the connection between circular permutation and
the loss of cooperativity experimentally observed
Representative structures of the most populated clusters.
<p>The clustering algorithm was applied during the last 100-NMR and MD-XR trajectories are shown in light and dark colors, respectively. The color code for the different protein segments is the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074383#pone-0074383-g001" target="_blank">Figure 1</a>.</p