972 research outputs found
Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension
Because of the potential link between -1 programmed ribosomal frameshifting
and response of a pseudoknot (PK) RNA to force, a number of single molecule
pulling experiments have been performed on PKs to decipher the mechanism of
programmed ribosomal frameshifting. Motivated in part by these experiments, we
performed simulations using a coarse-grained model of RNA to describe the
response of a PK over a range of mechanical forces (s) and monovalent salt
concentrations (s). The coarse-grained simulations quantitatively reproduce
the multistep thermal melting observed in experiments, thus validating our
model. The free energy changes obtained in simulations are in excellent
agreement with experiments. By varying and , we calculated the phase
diagram that shows a sequence of structural transitions, populating distinct
intermediate states. As and are changed, the stem-loop tertiary
interactions rupture first, followed by unfolding of the -end
hairpin (). Finally, the
-end hairpin unravels, producing an extended state
(). A theoretical analysis of the phase
boundaries shows that the critical force for rupture scales as with for
() transition. This relation is used to
obtain the preferential ion-RNA interaction coefficient, which can be
quantitatively measured in single-molecule experiments, as done previously for
DNA hairpins. A by-product of our work is the suggestion that the frameshift
efficiency is likely determined by the stability of the -end
hairpin that the ribosome first encounters during translation.Comment: Final draft accepted in Journal of Molecular Biology, 16 pages
including Supporting Informatio
Probing protein-protein interactions by dynamic force correlated spectroscopy (FCS)
We develop a formalism for single molecule dynamic force spectroscopy to map
the energy landscape of protein-protein complex (). The joint
distribution of unbinding lifetimes and
measurable in a compression-tension cycle, which accounts for the internal
relaxation dynamics of the proteins under tension, shows that the histogram of
is not Poissonian. The theory is applied to the forced unbinding of
protein , modeled as a wormlike chain, from . We propose a new
class of experiments which can resolve the effect of internal protein dynamics
on the unbinding lifetimes.Comment: 12 pages, 3 figures, accepted to Phys. Rev. Let
Viscosity Dependence of the Folding Rates of Proteins
The viscosity dependence of the folding rates for four sequences (the native
state of three sequences is a beta-sheet, while the fourth forms an
alpha-helix) is calculated for off-lattice models of proteins. Assuming that
the dynamics is given by the Langevin equation we show that the folding rates
increase linearly at low viscosities \eta, decrease as 1/\eta at large \eta and
have a maximum at intermediate values. The Kramers theory of barrier crossing
provides a quantitative fit of the numerical results. By mapping the simulation
results to real proteins we estimate that for optimized sequences the time
scale for forming a four turn \alpha-helix topology is about 500 nanoseconds,
whereas the time scale for forming a beta-sheet topology is about 10
microseconds.Comment: 14 pages, Latex, 3 figures. One figure is also available at
http://www.glue.umd.edu/~klimov/seq_I_H.html, to be published in Physical
Review Letter
Comment on "Chain Length Scaling of Protein Folding Time", PRL 77, 5433 (1996)
In a recent Letter, Gutin, Abkevich, and Shakhnovich (GAS) reported on a
series of dynamical Monte Carlo simulations on lattice models of proteins.
Based on these highly simplified models, they found that four different
potential energies lead to four different folding time scales tau_f, where
tau_f scales with chain length as N^lambda (see, also, Refs. [2-4]), with
lambda varying from 2.7 to 6.0. However, due to the lack of microscopic models
of protein folding dynamics, the interpretation and origin of the data have
remained somewhat speculative. It is the purpose of this Comment to point out
that the application of a simple "mesoscopic" model (cond-mat/9512019, PRL 77,
2324, 1996) of protein folding provides a full account of the data presented in
their paper. Moreover, we find a major qualitative disagreement with the
argumentative interpretation of GAS. Including, the origin of the dynamics, and
size of the critical folding nucleus.Comment: 1 page Revtex, 1 fig. upon request. Submitted to PR
Gaussian resolutions for equilibrium density matrices
A Gaussian resolution method for the computation of equilibrium density
matrices rho(T) for a general multidimensional quantum problem is presented.
The variational principle applied to the ``imaginary time'' Schroedinger
equation provides the equations of motion for Gaussians in a resolution of
rho(T) described by their width matrix, center and scale factor, all treated as
dynamical variables.
The method is computationally very inexpensive, has favorable scaling with
the system size and is surprisingly accurate in a wide temperature range, even
for cases involving quantum tunneling. Incorporation of symmetry constraints,
such as reflection or particle statistics, is also discussed.Comment: 4 page
Fractal Analysis of Protein Potential Energy Landscapes
The fractal properties of the total potential energy V as a function of time
t are studied for a number of systems, including realistic models of proteins
(PPT, BPTI and myoglobin). The fractal dimension of V(t), characterized by the
exponent \gamma, is almost independent of temperature and increases with time,
more slowly the larger the protein. Perhaps the most striking observation of
this study is the apparent universality of the fractal dimension, which depends
only weakly on the type of molecular system. We explain this behavior by
assuming that fractality is caused by a self-generated dynamical noise, a
consequence of intermode coupling due to anharmonicity. Global topological
features of the potential energy landscape are found to have little effect on
the observed fractal behavior.Comment: 17 pages, single spaced, including 12 figure
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