754 research outputs found
Stretching Single Domain Proteins: Phase Diagram and Kinetics of Force-Induced Unfolding
Single molecule force spectroscopy reveals unfolding of domains in titin upon
stretching. We provide a theoretical framework for these experiments by
computing the phase diagrams for force-induced unfolding of single domain
proteins using lattice models. The results show that two-state folders (at zero
force) unravel cooperatively whereas stretching of non-two-state folders occurs
through intermediates. The stretching rates of individual molecules show great
variations reflecting the heterogeneity of force-induced unfolding pathways.
The approach to the stretched state occurs in a step-wise "quantized" manner.
Unfolding dynamics depends sensitively on topology. The unfolding rates
increase exponentially with force f till an optimum value which is determined
by the barrier to unfolding when f=0. A mapping of these results to proteins
shows qualitative agreement with force-induced unfolding of Ig-like domains in
titin. We show that single molecule force spectroscopy can be used to map the
folding free energy landscape of proteins in the absence of denaturants.Comment: 12 pages, Latex, 6 ps figure
Different pathways in mechanical unfolding/folding cycle of a single semiflexible polymer
Kinetics of conformational change of a semiflexible polymer under mechanical
external field were investigated with Langevin dynamics simulations. It is
found that a semiflexible polymer exhibits large hysteresis in mechanical
folding/unfolding cycle even with a slow operation, whereas in a flexible
polymer, the hysteresis almost disappears at a sufficiently slow operation.
This suggests that the essential features of the structural transition of a
semiflexible polymer should be interpreted at least on a two-dimensional phase
space. The appearance of such large hysteresis is discussed in relation to
different pathways in the loading and unloading processes. By using a minimal
two-variable model, the hysteresis loop is described in terms of different
pathways on the transition between two stable states.Comment: 19 pages, 5 figure
Reversible stretching of homopolymers and random heteropolymers
We have analyzed the equilibrium response of chain molecules to stretching.
For a homogeneous sequence of monomers, the induced transition from compact
globule to extended coil below the -temperature is predicted to be
sharp. For random sequences, however, the transition may be smoothed by a
prevalence of necklace-like structures, in which globular regions and coil
regions coexist in a single chain. As we show in the context of a random
copolymer, preferential solvation of one monomer type lends stability to such
structures. The range of stretching forces over which necklaces are stable is
sensitive to chain length as well as sequence statistics.Comment: 14 pages, 4 figure
Extracting Structural Information of a Heteropolymer from Force-Extension Curves
We present a theory for the reverse analysis on the sequence information of a
single H/P two-letter random hetero-polymer (RHP) from its force-extension(f-z)
curves during quasi static stretching. Upon stretching of a self-assembled RHP,
it undergoes several structural transitions. The typical elastic response of a
hetero-polymeric globule is a set of overlapping saw-tooth patterns. With
consideration of the height and the position of the overlapping saw-tooth
shape, we analyze the possibility of extracting the binding energies of the
internal domains and the corresponding block sizes of the contributing
conformations.Comment: 5 figures 7 page
DNA unzipped under a constant force exhibits multiple metastable intermediates
Single molecule studies, at constant force, of the separation of
double-stranded DNA into two separated single strands may provide information
relevant to the dynamics of DNA replication. At constant applied force, theory
predicts that the unzipped length as a function of time is characterized by
jumps during which the strands separate rapidly, followed by long pauses where
the number of separated base pairs remains constant. Here, we report previously
uncharacterized observations of this striking behavior carried out on a number
of identical single molecules simultaneously. When several single lphage
molecules are subject to the same applied force, the pause positions are
reproducible in each. This reproducibility shows that the positions and
durations of the pauses in unzipping provide a sequence-dependent molecular
fingerprint. For small forces, the DNA remains in a partially unzipped state
for at least several hours. For larger forces, the separation is still
characterized by jumps and pauses, but the double-stranded DNA will completely
unzip in less than 30 min
Thermal Fluctuations of Elastic Filaments with Spontaneous Curvature and Torsion
We study the effects of thermal flucutations on thin elastic filaments with
spontaneous curvature and torsion. We derive analytical expressions for the
orientational correlation functions and for the persistence length of helices,
and find that this length varies non-monotonically with the strength of thermal
fluctuations. In the weak fluctuation regime, the persistence length of a
spontaneously twisted helix has three resonance peaks as a function of the
twist rate. In the limit of strong fluctuations, all memory of the helical
shape is lost.Comment: 1 figur
Single Molecule Statistics and the Polynucleotide Unzipping Transition
We present an extensive theoretical investigation of the mechanical unzipping
of double-stranded DNA under the influence of an applied force. In the limit of
long polymers, there is a thermodynamic unzipping transition at a critical
force value of order 10 pN, with different critical behavior for homopolymers
and for random heteropolymers. We extend results on the disorder-averaged
behavior of DNA's with random sequences to the more experimentally accessible
problem of unzipping a single DNA molecule. As the applied force approaches the
critical value, the double-stranded DNA unravels in a series of discrete,
sequence-dependent steps that allow it to reach successively deeper energy
minima. Plots of extension versus force thus take the striking form of a series
of plateaus separated by sharp jumps. Similar qualitative features should
reappear in micromanipulation experiments on proteins and on folded RNA
molecules. Despite their unusual form, the extension versus force curves for
single molecules still reveal remnants of the disorder-averaged critical
behavior. Above the transition, the dynamics of the unzipping fork is related
to that of a particle diffusing in a random force field; anomalous,
disorder-dominated behavior is expected until the applied force exceeds the
critical value for unzipping by roughly 5 pN.Comment: 40 pages, 18 figure
Theory of biopolymer stretching at high forces
We provide a unified theory for the high force elasticity of biopolymers
solely in terms of the persistence length, , and the monomer spacing,
. When the force f>\fh \sim k_BT\xi_p/a^2 the biopolymers behave as Freely
Jointed Chains (FJCs) while in the range \fl \sim k_BT/\xi_p < f < \fh the
Worm-like Chain (WLC) is a better model. We show that can be estimated
from the force extension curve (FEC) at the extension
(normalized by the contour length of the biopolymer). After validating the
theory using simulations, we provide a quantitative analysis of the FECs for a
diverse set of biopolymers (dsDNA, ssRNA, ssDNA, polysaccharides, and
unstructured PEVK domain of titin) for . The success of a specific
polymer model (FJC or WLC) to describe the FEC of a given biopolymer is
naturally explained by the theory. Only by probing the response of biopolymers
over a wide range of forces can the -dependent elasticity be fully
described.Comment: 20 pages, 4 figure
Force-Extension Relations for Polymers with Sliding Links
Topological entanglements in polymers are mimicked by sliding rings
(slip-links) which enforce pair contacts between monomers. We study the
force-extension curve for linear polymers in which slip-links create additional
loops of variable size. For a single loop in a phantom chain, we obtain exact
expressions for the average end-to-end separation: The linear response to a
small force is related to the properties of the unstressed chain, while for a
large force the polymer backbone can be treated as a sequence of Pincus--de
Gennes blobs, the constraint effecting only a single blob. Generalizing this
picture, scaling arguments are used to include self-avoiding effects.Comment: 4 pages, 5 figures; accepted to Phys. Rev. E (Brief Report
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