202 research outputs found
Direction dependent mechanical unfolding and Green Fluorescent Protein as a force sensor
An Ising--like model of proteins is used to investigate the mechanical
unfolding of the Green Fluorescent Protein along different directions. When the
protein is pulled from its ends, we recover the major and minor unfolding
pathways observed in experiments. Upon varying the pulling direction, we find
the correct order of magnitude and ranking of the unfolding forces. Exploiting
the direction dependence of the unfolding force at equilibrium, we propose a
force sensor whose luminescence depends on the applied force.Comment: to appear in Phys Rev
Downhill versus two-state protein folding in a statistical mechanical model
The authors address the problem of downhill protein folding in the framework
of a simple statistical mechanical model, which allows an exact solution for
the equilibrium and a semianalytical treatment of the kinetics. Focusing on
protein 1BBL, a candidate for downhill folding behavior, and comparing it to
the WW domain of protein PIN1, a two-state folder of comparable size, the
authors show that there are qualitative differences in both the equilibrium and
kinetic properties of the two molecules. However, the barrierless scenario
which would be expected if 1BBL were a true downhill folder is observed only at
low enough temperature.Comment: 20 pages, 13 figure
Protein mechanical unfolding: a model with binary variables
A simple lattice model, recently introduced as a generalization of the
Wako--Sait\^o model of protein folding, is used to investigate the properties
of widely studied molecules under external forces. The equilibrium properties
of the model proteins, together with their energy landscape, are studied on the
basis of the exact solution of the model. Afterwards, the kinetic response of
the molecules to a force is considered, discussing both force clamp and dynamic
loading protocols and showing that theoretical expectations are verified. The
kinetic parameters characterizing the protein unfolding are evaluated by using
computer simulations and agree nicely with experimental results, when these are
available. Finally, the extended Jarzynski equality is exploited to investigate
the possibility of reconstructing the free energy landscape of proteins with
pulling experiments
Equilibrium properties and force-driven unfolding pathways of RNA molecules
The mechanical unfolding of a simple RNA hairpin and of a 236--bases portion
of the Tetrahymena thermophila ribozyme is studied by means of an Ising--like
model. Phase diagrams and free energy landscapes are computed exactly and
suggest a simple two--state behaviour for the hairpin and the presence of
intermediate states for the ribozyme. Nonequilibrium simulations give the
possible unfolding pathways for the ribozyme, and the dominant pathway
corresponds to the experimentally observed one.Comment: Main text + appendix, to appear in Phys. Rev. Let
Effects of confinement on thermal stability and folding kinetics in a simple Ising-like model
In cellular environment, confinement and macromulecular crowding play an
important role on thermal stability and folding kinetics of a protein. We have
resorted to a generalized version of the Wako-Saito-Munoz-Eaton model for
protein folding to study the behavior of six different protein structures
confined between two walls. Changing the distance 2R between the walls, we
found, in accordance with previous studies, two confinement regimes: starting
from large R and decreasing R, confinement first enhances the stability of the
folded state as long as this is compact and until a given value of R; then a
further decrease of R leads to a decrease of folding temperature and folding
rate. We found that in the low confinement regime both unfolding temperatures
and logarithm of folding rates scale as R-{\gamma} where {\gamma} values lie in
between 1.42 and 2.35
Analysis of the Equilibrium and Kinetics of the Ankyrin Repeat Protein Myotrophin
We apply the Wako-Saito-Munoz-Eaton model to the study of Myotrophin, a small
ankyrin repeat protein, whose folding equilibrium and kinetics have been
recently characterized experimentally. The model, which is a native-centric
with binary variables, provides a finer microscopic detail than the Ising
model, that has been recently applied to some different repeat proteins, while
being still amenable for an exact solution. In partial agreement with the
experiments, our results reveal a weakly three-state equilibrium and a
two-state-like kinetics of the wild type protein despite the presence of a
non-trivial free-energy profile. These features appear to be related to a
careful "design" of the free-energy landscape, so that mutations can alter this
picture, stabilizing some intermediates and changing the position of the
rate-limiting step. Also the experimental findings of two alternative pathways,
an N-terminal and a C-terminal one, are qualitatively confirmed, even if the
variations in the rates upon the experimental mutations cannot be
quantitatively reproduced. Interestingly, folding and unfolding pathway appear
to be different, even if closely related: a property that is not generally
considered in the phenomenological interpretation of the experimental data.Comment: 27 pages, 7 figure
Cluster variation - Pade` approximants method for the simple cubic Ising model
The cluster variation - Pade` approximant method is a recently proposed tool,
based on the extrapolation of low/high temperature results obtained with the
cluster variation method, for the determination of critical parameters in
Ising-like models. Here the method is applied to the three-dimensional simple
cubic Ising model, and new results, obtained with an 18-site basic cluster, are
reported. Other techniques for extracting non-classical critical exponents are
also applied and their results compared with those by the cluster variation -
Pade` approximant method.Comment: 8 RevTeX pages, 3 PostScript figure
On the low-temperature phase of the three-state antiferromagnetic Potts model on the simple cubic lattice
The three-state antiferromagnetic Potts model on the simple cubic lattice is
investigated using the cluster variation method in the cube and the star-cube
approximations. The broken-sublattice-symmetry phase is found to be stable in
the whole low-temperature region, contrary to previous results obtained using a
modified cluster variation method. The tiny free energy difference between the
broken-sublattice-symmetry and the permutationally-symmetric-sublattices phases
is calculated in the two approximations and turns out to be smaller in the
(more accurate) star-cube approximation than in the cube one.Comment: 4 pages REVTeX + 2 PostScript figures, to be published in Phys. Rev.
E as a Rapid Communicatio
An exactly solvable model for a beta-hairpin with random interactions
I investigate a disordered version of a simplified model of protein folding,
with binary degrees of freedom, applied to an ideal beta-hairpin structure.
Disorder is introduced by assuming that the contact energies are independent
and identically distributed random variables. The equilibrium free-energy of
the model is studied, performing the exact calculation of its quenched value
and proving the self-averaging feature.Comment: 9 page
Rate Determining Factors in Protein Model Structures
Previous research has shown a strong correlation of protein folding rates to
the native state geometry, yet a complete explanation for this dependence is
still lacking. Here we study the rate-geometry relationship with a simple
statistical physics model, and focus on two classes of model geometries,
representing ideal parallel and antiparallel structures. We find that the
logarithm of the rate shows an almost perfect linear correlation with the
"absolute contact order", but the slope depends on the particular class
considered. We discuss these findings in the light of experimental results.Comment: 4 pages, 2 figure
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