1887
banner image
No data available.
Please log in to see this content.
You have no subscription access to this content.
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.
Computer simulations of the translocation and unfolding of a protein pulled mechanically through a pore
Rent:
Rent this article for
USD
10.1063/1.2008231
/content/aip/journal/jcp/123/12/10.1063/1.2008231
http://aip.metastore.ingenta.com/content/aip/journal/jcp/123/12/10.1063/1.2008231
View: Figures

Figures

Image of FIG. 1.
FIG. 1.

(Color online) Comparison of the mechanical stretching and translocation of ubiquitin. The mechanical stretching reaction coordinate is the component of the end-to-end distance vector in the direction of the stretching force. The translocation coordinate is the displacement of the chain end along the axis of the cylindrical pore, relative to the pore entrance. The force applied to this end acts along the axis. The translocation and stretching reaction coordinates will coincide when the tail of the peptide chain is aligned with the pore entrance. The plots of protein structures here and in other figures were created by using the PYMOL software. (Ref. 36).

Image of FIG. 2.
FIG. 2.

(Color online) Mechanical unfolding of ubiquitin (Ref. 27). The potential of mean force is plotted as a function of the mechanical stretching reaction coordinate at different values of the stretching force. The free energy is measured in units of , which represents a typical strength of hydrophobic interactions (see Sec. II). The force is measured in dimensionless units of , where is the distance between the neighboring atoms in the polypeptide chain. For a unit of force corresponds to . The minima of correspond to the nativelike state 0 and the unfolding intermediates 1 and 2. The structure of these intermediates is shown along with the corresponding contact maps, which are the plots of contacting pairs of residues such that . Near-neighbor contacts are excluded from the maps. The darkness of each point reflects the probability of observing the corresponding contact in the equilibrium ensemble of conformations corresponding to the given extension , black corresponding to the highest probability. Secondary structures (helices and strands), to which residues and belong, are shown along the and axes so that clusters of contacts on the map correspond to the proximity of secondary structure elements.

Image of FIG. 3.
FIG. 3.

(Color online) Translocation of ubiquitin driven by a mechanical force applied at the -terminus of the chain. The potential of mean force is plotted as a function of the translocation coordinate equal to the position of the -end of the chain along the pore at different values of the stretching force. The pore radius is . The free energy is measured in units of and the force is measured in units of (see Sec. II). For . The minima of correspond to translocation intermediates 1–3, whose structure is shown along with the corresponding contact maps. The nativelike structure 0 not shown here is similar to structure 0 shown in Fig. 2. For low force, the rate-limiting step is late in the translocation process and corresponds to the transition between structure 3 and the extended state. For high force, the rate-limiting step of translocation corresponds to the transition between structures 1 and 2.

Image of FIG. 4.
FIG. 4.

(Color online) Translocation of ubiquitin driven by a mechanical force applied at the -terminus of the chain. The potential of mean force is plotted as a function of the translocation coordinate equal to the position of the -end of the chain along the pore at three different values of the stretching force. The pore radius is . The free energy is measured in units of and the force is measured in units of (see Sec. II). The structure of representative translocation intermediates 1–3 corresponding to local minima of is depicted and contact maps corresponding to those intermediates are plotted. The nativelike structure 0 is shown in Fig. 2. For high forces, the rate-limiting step of translocation corresponds to the transition between structures 1 and 2.

Image of FIG. 5.
FIG. 5.

The overall speed of the translocation/unfolding process. The unfolding barrier [defined as the difference between the maximum and the minimum of ] is plotted as a function of the pulling force applied to the -terminus (solid line) and -terminus (dashed line). Crudely speaking, this barrier determines the overall rate of the translocation process so that the plot of vs represents the dependence of the logarithm of the rate of translocation on the force (aside from a shift and a scaling factor). The free energy is measured in units of and the force is measured in units of (see Sec. II).

Image of FIG. 6.
FIG. 6.

The potential of mean force for different values of the pore diameter.

Image of FIG. 7.
FIG. 7.

(Color online) Translocation of ubiquitin across a wide pore . The potential of mean force is plotted as a function of the translocation coordinate equal to the position of the -end of the chain along the pore at different values of the stretching force. Also shown are representative structures encountered in the course of translocation along with the corresponding contact maps.

Loading

Article metrics loading...

/content/aip/journal/jcp/123/12/10.1063/1.2008231
2005-09-23
2014-04-20
Loading

Full text loading...

This is a required field
Please enter a valid email address
752b84549af89a08dbdd7fdb8b9568b5 journal.articlezxybnytfddd
Scitation: Computer simulations of the translocation and unfolding of a protein pulled mechanically through a pore
http://aip.metastore.ingenta.com/content/aip/journal/jcp/123/12/10.1063/1.2008231
10.1063/1.2008231
SEARCH_EXPAND_ITEM