2,286 research outputs found
Highly Designable Protein Structures and Inter Monomer Interactions
By exact computer enumeration and combinatorial methods, we have calculated
the designability of proteins in a simple lattice H-P model for the protein
folding problem.
We show that if the strength of the non-additive part of the interaction
potential becomes larger than a critical value, the degree of designability of
structures will depend on the parameters of potential. We also show that the
existence of a unique ground state is highly sensitive to mutation in certain
sites.Comment: 14 pages, Latex file, 3 latex and 6 eps figures are include
A possible mechanism for cold denaturation of proteins at high pressure
We study cold denaturation of proteins at high pressures. Using
multicanonical Monte Carlo simulations of a model protein in a water bath, we
investigate the effect of water density fluctuations on protein stability. We
find that above the pressure where water freezes to the dense ice phase
( kbar), the mechanism for cold denaturation with decreasing
temperature is the loss of local low-density water structure. We find our
results in agreement with data of bovine pancreatic ribonuclease A.Comment: 4 pages for double column and single space. 3 figures Added
references Changed conten
One-dimensional Ising ferromagnet frustrated by long-range interactions at finite temperatures
We consider a one-dimensional lattice of Ising-type variables where the
ferromagnetic exchange interaction J between neighboring sites is frustrated by
a long-ranged anti-ferromagnetic interaction of strength g between the sites i
and j, decaying as |i-j|^-alpha, with alpha>1. For alpha smaller than a certain
threshold alpha_0, which is larger than 2 and depends on the ratio J/g, the
ground state consists of an ordered sequence of segments with equal length and
alternating magnetization. The width of the segments depends on both alpha and
the ratio J/g. Our Monte Carlo study shows that the on-site magnetization
vanishes at finite temperatures and finds no indication of any phase
transition. Yet, the modulation present in the ground state is recovered at
finite temperatures in the two-point correlation function, which oscillates in
space with a characteristic spatial period: The latter depends on alpha and J/g
and decreases smoothly from the ground-state value as the temperature is
increased. Such an oscillation of the correlation function is exponentially
damped over a characteristic spatial scale, the correlation length, which
asymptotically diverges roughly as the inverse of the temperature as T=0 is
approached. This suggests that the long-range interaction causes the Ising
chain to fall into a universality class consistent with an underlying
continuous symmetry. The e^(Delta/T)-temperature dependence of the correlation
length and the uniform ferromagnetic ground state, characteristic of the g=0
discrete Ising symmetry, are recovered for alpha > alpha_0.Comment: 12 pages, 7 figure
From Collapse to Freezing in Random Heteropolymers
We consider a two-letter self-avoiding (square) lattice heteropolymer model
of N_H (out ofN) attracting sites. At zero temperature, permanent links are
formed leading to collapse structures for any fraction rho_H=N_H/N. The average
chain size scales as R = N^{1/d}F(rho_H) (d is space dimension). As rho_H -->
0, F(rho_H) ~ rho_H^z with z={1/d-nu}=-1/4 for d=2. Moreover, for 0 < rho_H <
1, entropy approaches zero as N --> infty (being finite for a homopolymer). An
abrupt decrease in entropy occurs at the phase boundary between the swollen (R
~ N^nu) and collapsed region. Scaling arguments predict different regimes
depending on the ensemble of crosslinks. Some implications to the protein
folding problem are discussed.Comment: 4 pages, Revtex, figs upon request. New interpretation and emphasis.
Submitted to Europhys.Let
Exploring the Levinthal limit in protein folding
According to the thermodynamic hypothesis, the native state of proteins is uniquely defined by their amino acid sequence. On the other hand, according to Levinthal, the native state is just a local minimum of the free energy and a given amino acid sequence, in the same thermodynamic conditions, can assume many, very different structures that are as thermodynamically stable as the native state. This is the Levinthal limit explored in this work. Using computer simulations, we compare the interactions that stabilize the native state of four different proteins with those that stabilize three non-native states of each protein and find that the nature of the interactions is very similar for all such 16 conformers. Furthermore, an enhancement of the degree of fluctuation of the non-native conformers can be explained by an insufficient relaxation to their local free energy minimum. These results favor Levinthal's hypothesis that protein folding is a kinetic non-equilibrium process.FCT - Foundation for Science and Technology, Portugal [UID/Multi/04326/2013]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientia co e Tecnologico (CNPq
Finite size effects on thermal denaturation of globular proteins
Finite size effects on the cooperative thermal denaturation of proteins are
considered. A dimensionless measure of cooperativity, Omega, scales as N^zeta,
where N is the number of amino acids. Surprisingly, we find that zeta is
universal with zeta = 1 + gamma, where the exponent gamma characterizes the
divergence of the susceptibility for a self-avoiding walk. Our lattice model
simulations and experimental data are consistent with the theory. Our finding
rationalizes the marginal stability of proteins and substantiates the earlier
predictions that the efficient folding of two-state proteins requires the
folding transition temperature to be close to the collapse temperature.Comment: 3 figures. Physical Review Letters (in press
Energetic Components of Cooperative Protein Folding
A new lattice protein model with a four-helix bundle ground state is analyzed
by a parameter-space Monte Carlo histogram technique to evaluate the effects of
an extensive variety of model potentials on folding thermodynamics. Cooperative
helical formation and contact energies based on a 5-letter alphabet are found
to be insufficient to satisfy calorimetric and other experimental criteria for
two-state folding. Such proteinlike behaviors are predicted, however, by models
with polypeptide-like local conformational restrictions and
environment-dependent hydrogen bonding-like interactions.Comment: 11 pages, 4 postscripts figures, Phys. Rev. Lett. (in press
Theta-point universality of polyampholytes with screened interactions
By an efficient algorithm we evaluate exactly the disorder-averaged
statistics of globally neutral self-avoiding chains with quenched random charge
in monomer i and nearest neighbor interactions on
square (22 monomers) and cubic (16 monomers) lattices. At the theta transition
in 2D, radius of gyration, entropic and crossover exponents are well compatible
with the universality class of the corresponding transition of homopolymers.
Further strong indication of such class comes from direct comparison with the
corresponding annealed problem. In 3D classical exponents are recovered. The
percentage of charge sequences leading to folding in a unique ground state
approaches zero exponentially with the chain length.Comment: 15 REVTEX pages. 4 eps-figures . 1 tabl
Ground state and glass transition of the RNA secondary structure
RNA molecules form a sequence-specific self-pairing pattern at low
temperatures. We analyze this problem using a random pairing energy model as
well as a random sequence model that includes a base stacking energy in favor
of helix propagation. The free energy cost for separating a chain into two
equal halves offers a quantitative measure of sequence specific pairing. In the
low temperature glass phase, this quantity grows quadratically with the
logarithm of the chain length, but it switches to a linear behavior of entropic
origin in the high temperature molten phase. Transition between the two phases
is continuous, with characteristics that resemble those of a disordered elastic
manifold in two dimensions. For designed sequences, however, a power-law
distribution of pairing energies on a coarse-grained level may be more
appropriate. Extreme value statistics arguments then predict a power-law growth
of the free energy cost to break a chain, in agreement with numerical
simulations. Interestingly, the distribution of pairing distances in the ground
state secondary structure follows a remarkable power-law with an exponent -4/3,
independent of the specific assumptions for the base pairing energies
Protein sequence and structure: Is one more fundamental than the other?
We argue that protein native state structures reside in a novel "phase" of
matter which confers on proteins their many amazing characteristics. This phase
arises from the common features of all globular proteins and is characterized
by a sequence-independent free energy landscape with relatively few low energy
minima with funnel-like character. The choice of a sequence that fits well into
one of these predetermined structures facilitates rapid and cooperative
folding. Our model calculations show that this novel phase facilitates the
formation of an efficient route for sequence design starting from random
peptides.Comment: 7 pages, 4 figures, to appear in J. Stat. Phy
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