215 research outputs found
Mapping of mutation-sensitive sites in protein-like chains
In this work we have studied, with the help of a simple on-lattice model, the
distribution pattern of sites sensitive to point mutations ('hot' sites) in
protein-like chains. It has been found that this pattern depends on the
regularity of the matrix that rules the interaction between different kinds of
residues. If the interaction matrix is dominated by the hydrophobic effect
(Miyazawa Jernigan like matrix), this distribution is very simple - all the
'hot' sites can be found at the positions with maximum number of closest
nearest neighbors (bulk).
If random or nonlinear corrections are added to such an interaction matrix
the distribution pattern changes. The rising of collective effects allows the
'hot' sites to be found in places with smaller number of nearest neighbors
(surface) while the general trend of the 'hot' sites to fall into a bulk part
of a conformation still holds.Comment: 15 pages, 6 figure
Designability of lattice model heteropolymers
Protein folds are highly designable, in the sense that many sequences fold to
the same conformation. In the present work we derive an expression for the
designability in a 20 letter lattice model of proteins which, relying only on
the Central Limit Theorem, has a generality which goes beyond the simple model
used in its derivation. This expression displays an exponential dependence on
the energy of the optimal sequence folding on the given conformation measured
with respect to the lowest energy of the conformational dissimilar structures,
energy difference which constitutes the only parameter controlling
designability. Accordingly, the designability of a native conformation is
intimately connected to the stability of the sequences folding to them.Comment: in press on Phys. Rev.
Is Heteropolymer Freezing Well Described by the Random Energy Model?
It is widely held that the Random Energy Model (REM) describes the freezing
transition of a variety of types of heteropolymers. We demonstrate that the
hallmark property of REM, statistical independence of the energies of states
over disorder, is violated in different ways for models commonly employed in
heteropolymer freezing studies. The implications for proteins are also
discussed.Comment: 4 pages, 3 eps figures To appear in Physical Review Letters, May 199
Two-Dimensional Polymers with Random Short-Range Interactions
We use complete enumeration and Monte Carlo techniques to study
two-dimensional self-avoiding polymer chains with quenched ``charges'' .
The interaction of charges at neighboring lattice sites is described by . We find that a polymer undergoes a collapse transition at a temperature
, which decreases with increasing imbalance between charges. At the
transition point, the dependence of the radius of gyration of the polymer on
the number of monomers is characterized by an exponent , which is slightly larger than the similar exponent for homopolymers. We
find no evidence of freezing at low temperatures.Comment: 4 two-column pages, 6 eps figures, RevTex, Submitted to Phys. Rev.
Freezing Transition of Random Heteropolymers Consisting of an Arbitrary Set of Monomers
Mean field replica theory is employed to analyze the freezing transition of
random heteropolymers comprised of an arbitrary number () of types of
monomers. Our formalism assumes that interactions are short range and
heterogeneity comes only from pairwise interactions, which are defined by an
arbitrary matrix. We show that, in general, there exists a
freezing transition from a random globule, in which the thermodynamic
equilibrium is comprised of an essentially infinite number polymer
conformations, to a frozen globule, in which equilibrium ensemble is dominated
by one or very few conformations. We also examine some special cases of
interaction matrices to analyze the relationship between the freezing
transition and the nature of interactions involved.Comment: 30 pages, 1 postscript figur
Modeling study on the validity of a possibly simplified representation of proteins
The folding characteristics of sequences reduced with a possibly simplified
representation of five types of residues are shown to be similar to their
original ones with the natural set of residues (20 types or 20 letters). The
reduced sequences have a good foldability and fold to the same native structure
of their optimized original ones. A large ground state gap for the native
structure shows the thermodynamic stability of the reduced sequences. The
general validity of such a five-letter reduction is further studied via the
correlation between the reduced sequences and the original ones. As a
comparison, a reduction with two letters is found not to reproduce the native
structure of the original sequences due to its homopolymeric features.Comment: 6 pages with 4 figure
Deviations from the mean field predictions for the phase behaviour of random copolymers melts
We investigate the phase behaviour of random copolymers melts via large scale
Monte Carlo simulations. We observe macrophase separation into A and B--rich
phases as predicted by mean field theory only for systems with a very large
correlation lambda of blocks along the polymer chains, far away from the
Lifshitz point. For smaller values of lambda, we find that a locally
segregated, disordered microemulsion--like structure gradually forms as the
temperature decreases. As we increase the number of blocks in the polymers, the
region of macrophase separation further shrinks. The results of our Monte Carlo
simulation are in agreement with a Ginzburg criterium, which suggests that mean
field theory becomes worse as the number of blocks in polymers increases.Comment: 6 pages, 4 figures, Late
Correlated disorder in random block-copolymers
We study the effect of a random Flory-Huggins parameter in a symmetric
diblock copolymer melt which is expected to occur in a copolymer where one
block is near its structural glass transition. In the clean limit the
microphase segregation between the two blocks causes a weak, fluctuation
induced first order transition to a lamellar state. Using a renormalization
group approach combined with the replica trick to treat the quenched disorder,
we show that beyond a critical disorder strength, that depends on the length of
the polymer chain, the character of the transition is changed. The system
becomes dominated by strong randomness and a glassy rather than an ordered
lamellar state occurs. A renormalization of the effective disorder distribution
leads to nonlocal disorder correlations that reflect strong compositional
fluctuation on the scale of the radius of gyration of the polymer chains. The
reason for this behavior is shown to be the chain length dependent role of
critical fluctuations, which are less important for shorter chains and become
increasingly more relevant as the polymer length increases and the clean first
order transition becomes weaker.Comment: 11 pages, 5 figures, submitted to PR
Origin of Native Driving Force in Protein Folding
We derive an expression with four adjustable parameters that reproduces well
the 20x20 Miyazawa-Jernigan potential matrix extracted from known protein
structures. The numerical values of the parameters can be approximately
computed from the surface tension of water, water-screened dipole interactions
between residues and water and among residues, and average exposures of
residues in folded proteins.Comment: LaTeX file, Postscript file; 4 pages, 1 figure (mij.eps), 2 table
Simple models of protein folding and of non--conventional drug design
While all the information required for the folding of a protein is contained
in its amino acid sequence, one has not yet learned how to extract this
information to predict the three--dimensional, biologically active, native
conformation of a protein whose sequence is known. Using insight obtained from
simple model simulations of the folding of proteins, in particular of the fact
that this phenomenon is essentially controlled by conserved (native) contacts
among (few) strongly interacting ("hot"), as a rule hydrophobic, amino acids,
which also stabilize local elementary structures (LES, hidden, incipient
secondary structures like --helices and --sheets) formed early
in the folding process and leading to the postcritical folding nucleus (i.e.,
the minimum set of native contacts which bring the system pass beyond the
highest free--energy barrier found in the whole folding process) it is possible
to work out a succesful strategy for reading the native structure of designed
proteins from the knowledge of only their amino acid sequence and of the
contact energies among the amino acids. Because LES have undergone millions of
years of evolution to selectively dock to their complementary structures, small
peptides made out of the same amino acids as the LES are expected to
selectively attach to the newly expressed (unfolded) protein and inhibit its
folding, or to the native (fluctuating) native conformation and denaturate it.
These peptides, or their mimetic molecules, can thus be used as effective
non--conventional drugs to those already existing (and directed at neutralizing
the active site of enzymes), displaying the advantage of not suffering from the
uprise of resistance
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