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How fast does a signal propagate through proteins?

Young HT, Edwards SA, Gräter F - PLoS ONE (2013)

Bottom Line: The question arises how fast such a signal propagates through the protein molecular scaffold.The force propagates along the backbone into the center of the chain on the picosecond scale.The speed of force propagation of [Formula: see text]50Å ps(-1) derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.

View Article: PubMed Central - PubMed

Affiliation: CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai, P. R. China ; Graduate School of Chinese Academy of Sciences, Beijing, P. R. China.

ABSTRACT
As the molecular basis of signal propagation in the cell, proteins are regulated by perturbations, such as mechanical forces or ligand binding. The question arises how fast such a signal propagates through the protein molecular scaffold. As a first step, we have investigated numerically the dynamics of force propagation through a single (Ala)[Formula: see text] protein following a sudden increase in the stretching forces applied to its end termini. The force propagates along the backbone into the center of the chain on the picosecond scale. Both conformational and tension dynamics are found in good agreement with a coarse-grained theory of force propagation through semiflexible polymers. The speed of force propagation of [Formula: see text]50Å ps(-1) derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.

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Force propagation along a polypeptide in water.(a) After first equilibrating an (Ala) polypeptide under a relatively low stretching force of  applied to both termini of the polypeptide, we then suddenly increase the stretching force by a factor of 10 to . As the polymer is straightened, backbone tension propagates from the two termini into the center of the chain. (b) Structure used in the MD simulation. The (Ala) polypeptide is surrounded by explicit solvent molecules. A constant force,  or  is applied to the terminal C- atoms, and the end-to-end distance  of the peptide is measured.
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pone-0064746-g001: Force propagation along a polypeptide in water.(a) After first equilibrating an (Ala) polypeptide under a relatively low stretching force of applied to both termini of the polypeptide, we then suddenly increase the stretching force by a factor of 10 to . As the polymer is straightened, backbone tension propagates from the two termini into the center of the chain. (b) Structure used in the MD simulation. The (Ala) polypeptide is surrounded by explicit solvent molecules. A constant force, or is applied to the terminal C- atoms, and the end-to-end distance of the peptide is measured.

Mentions: Unfortunately, force propagation is inherently difficult to measure experimentally. Doing so not only requires excellent time resolution, one also has to either introduce force-sensitive probes into the molecular backbone [13] or resort to indirect and difficult to interpret measures such as force-induced heat dissipation [14]. However, the very same rapidity acting as a roadblock to experimental investigation pushes the subject of force propagation into the realm of atomistic molecular dynamics (MD) simulations, a technique that is limited to very short time scales, but has proven useful for our understanding of protein dynamics [15]. In particular, a good agreement has been observed between experimental and simulated folding rates, suggesting the time scales of non-equilibrium processes investigated by MD simulations to be of a reasonable order of magnitude [16], [17]. We take advantage of this fact by combining atomistic MD simulations of an (Ala) homo-polypeptide under external stretching force with Force Distribution Analysis (FDA) [18], allowing us to track intramolecular forces with perfect temporal and spatial resolution (see Fig. 1).


How fast does a signal propagate through proteins?

Young HT, Edwards SA, Gräter F - PLoS ONE (2013)

Force propagation along a polypeptide in water.(a) After first equilibrating an (Ala) polypeptide under a relatively low stretching force of  applied to both termini of the polypeptide, we then suddenly increase the stretching force by a factor of 10 to . As the polymer is straightened, backbone tension propagates from the two termini into the center of the chain. (b) Structure used in the MD simulation. The (Ala) polypeptide is surrounded by explicit solvent molecules. A constant force,  or  is applied to the terminal C- atoms, and the end-to-end distance  of the peptide is measured.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675101&req=5

pone-0064746-g001: Force propagation along a polypeptide in water.(a) After first equilibrating an (Ala) polypeptide under a relatively low stretching force of applied to both termini of the polypeptide, we then suddenly increase the stretching force by a factor of 10 to . As the polymer is straightened, backbone tension propagates from the two termini into the center of the chain. (b) Structure used in the MD simulation. The (Ala) polypeptide is surrounded by explicit solvent molecules. A constant force, or is applied to the terminal C- atoms, and the end-to-end distance of the peptide is measured.
Mentions: Unfortunately, force propagation is inherently difficult to measure experimentally. Doing so not only requires excellent time resolution, one also has to either introduce force-sensitive probes into the molecular backbone [13] or resort to indirect and difficult to interpret measures such as force-induced heat dissipation [14]. However, the very same rapidity acting as a roadblock to experimental investigation pushes the subject of force propagation into the realm of atomistic molecular dynamics (MD) simulations, a technique that is limited to very short time scales, but has proven useful for our understanding of protein dynamics [15]. In particular, a good agreement has been observed between experimental and simulated folding rates, suggesting the time scales of non-equilibrium processes investigated by MD simulations to be of a reasonable order of magnitude [16], [17]. We take advantage of this fact by combining atomistic MD simulations of an (Ala) homo-polypeptide under external stretching force with Force Distribution Analysis (FDA) [18], allowing us to track intramolecular forces with perfect temporal and spatial resolution (see Fig. 1).

Bottom Line: The question arises how fast such a signal propagates through the protein molecular scaffold.The force propagates along the backbone into the center of the chain on the picosecond scale.The speed of force propagation of [Formula: see text]50Å ps(-1) derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.

View Article: PubMed Central - PubMed

Affiliation: CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai, P. R. China ; Graduate School of Chinese Academy of Sciences, Beijing, P. R. China.

ABSTRACT
As the molecular basis of signal propagation in the cell, proteins are regulated by perturbations, such as mechanical forces or ligand binding. The question arises how fast such a signal propagates through the protein molecular scaffold. As a first step, we have investigated numerically the dynamics of force propagation through a single (Ala)[Formula: see text] protein following a sudden increase in the stretching forces applied to its end termini. The force propagates along the backbone into the center of the chain on the picosecond scale. Both conformational and tension dynamics are found in good agreement with a coarse-grained theory of force propagation through semiflexible polymers. The speed of force propagation of [Formula: see text]50Å ps(-1) derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.

Show MeSH
Related in: MedlinePlus