246 research outputs found
A novel iterative strategy for protein design
We propose and discuss a novel strategy for protein design. The method is
based on recent theoretical advancements which showed the importance to treat
carefully the conformational free energy of designed sequences. In this work we
show how computational cost can be kept to a minimum by encompassing negative
design features, i.e. isolating a small number of structures that compete
significantly with the target one for being occupied at low temperature. The
method is succesfully tested on minimalist protein models and using a variety
of amino acid interaction potentials.Comment: 9 pages, 8 figure
Elucidation of the disulfide folding pathway of hirudin by a topology-based approach
A theoretical model for the folding of proteins containing disulfide bonds is
introduced. The model exploits the knowledge of the native state to favour the
progressive establishment of native interactions. At variance with traditional
approaches based on native topology, not all native bonds are treated in the
same way; in particular, a suitable energy term is introduced to account for
the special strength of disulfide bonds (irrespective of whether they are
native or not) as well as their ability to undergo intra-molecular reshuffling.
The model thus possesses the minimal ingredients necessary to investigated the
much debated issue of whether the re-folding process occurs through partially
structured intermediates with native or non-native disulfide bonds. This
strategy is applied to a context of particular interest, the re-folding process
of Hirudin, a thrombin-specific protease inhibitor, for which conflicting
folding pathways have been proposed. We show that the only two parameters in
the model (temperature and disulfide strength) can be tuned to reproduce well a
set of experimental transitions between species with different number of formed
disulfide. This model is then used to provide a characterisation of the folding
process and a detailed description of the species involved in the rate-limiting
step of Hirudin refolding.Comment: 14 pages, 9 figure
Structural motifs of biomolecules
Biomolecular structures are assemblies of emergent anisotropic building
modules such as uniaxial helices or biaxial strands. We provide an approach to
understanding a marginally compact phase of matter that is occupied by proteins
and DNA. This phase, which is in some respects analogous to the liquid crystal
phase for chain molecules, stabilizes a range of shapes that can be obtained by
sequence-independent interactions occurring intra- and intermolecularly between
polymeric molecules. We present a singularityfree self-interaction for a tube
in the continuum limit and show that this results in the tube being positioned
in the marginally compact phase. Our work provides a unified framework for
understanding the building blocks of biomolecules.Comment: 13 pages, 5 figure
Continuum model for polymers with finite thickness
We consider the continuum limit of a recently-introduced model for
discretized thick polymers, or tubes. We address both analytically and
numerically how the polymer thickness influences the decay of tangent-tangent
correlations and find how the persistence length scales with the thickness and
the torsional rigidity of the tube centerline. At variance with the worm-like
chain model, the phase diagram that we obtain for a continuous tube is richer;
in particular, for a given polymer thickness there exists a threshold value for
the centerline torsional rigidity separating a simple exponential decay of the
tangent-tangent correlation from an oscillatory one.Comment: 8 pages, 4 figures. Accepted for publication in J. Phys.
Roundoff-induced Coalescence of Chaotic Trajectories
Numerical experiments recently discussed in the literature show that
identical nonlinear chaotic systems linked by a common noise term (or signal)
may synchronize after a finite time. We study the process of synchronization as
function of precision of calculations. Two generic behaviors of the average
coalescence time are identified: exponential or linear. In both cases no
synchronization occurs if iterations are done with {\em infinite} precision.Comment: 6 pages, 3 postscript figures, to be published in Phys. Rev.
Cluster Variation Approach to the Random-Anisotropy Blume-Emery-Griffiths Model
The random--anisotropy Blume--Emery--Griffiths model, which has been proposed
to describe the critical behavior of He--He mixtures in a porous
medium, is studied in the pair approximation of the cluster variation method
extended to disordered systems. Several new features, with respect to mean
field theory, are found, including a rich ground state, a nonzero percolation
threshold, a reentrant coexistence curve and a miscibility gap on the high
He concentration side down to zero temperature. Furthermore, nearest
neighbor correlations are introduced in the random distribution of the
anisotropy, which are shown to be responsible for the raising of the critical
temperature with respect to the pure and uncorrelated random cases and
contribute to the detachment of the coexistence curve from the line.Comment: 14 pages (plain TeX) + 12 figures (PostScript, appended), Preprint
POLFIS-TH.02/9
Conformations of Proteins in Equilibrium
We introduce a simple theoretical approach for an equilibrium study of
proteins with known native state structures. We test our approach with results
on well-studied globular proteins, Chymotrypsin Inhibitor (2ci2), Barnase and
the alpha spectrin SH3 domain and present evidence for a hierarchical onset of
order on lowering the temperature with significant organization at the local
level even at high temperatures. A further application to the folding process
of HIV-1 protease shows that the model can be reliably used to identify key
folding sites that are responsible for the development of drug resistance .Comment: 6 pages, 3 eps figure
An exactly solvable coarse-grained model for species diversity
We present novel analytical results about ecosystem species diversity that
stem from a proposed coarse grained neutral model based on birth-death
processes. The relevance of the problem lies in the urgency for understanding
and synthesizing both theoretical results of ecological neutral theory and
empirical evidence on species diversity preservation. Neutral model of
biodiversity deals with ecosystems in the same trophic level where per-capita
vital rates are assumed to be species-independent. Close-form analytical
solutions for neutral theory are obtained within a coarse-grained model, where
the only input is the species persistence time distribution. Our results
pertain: the probability distribution function of the number of species in the
ecosystem both in transient and stationary states; the n-points connected time
correlation function; and the survival probability, definned as the
distribution of time-spans to local extinction for a species randomly sampled
from the community. Analytical predictions are also tested on empirical data
from a estuarine fish ecosystem. We find that emerging properties of the
ecosystem are very robust and do not depend on specific details of the model,
with implications on biodiversity and conservation biology.Comment: 20 pages, 4 figures. To appear in Journal of Statistichal Mechanic
Optimal shapes of compact strings
Optimal geometrical arrangements, such as the stacking of atoms, are of
relevance in diverse disciplines. A classic problem is the determination of the
optimal arrangement of spheres in three dimensions in order to achieve the
highest packing fraction; only recently has it been proved that the answer for
infinite systems is a face-centred-cubic lattice. This simply stated problem
has had a profound impact in many areas, ranging from the crystallization and
melting of atomic systems, to optimal packing of objects and subdivision of
space. Here we study an analogous problem--that of determining the optimal
shapes of closely packed compact strings. This problem is a mathematical
idealization of situations commonly encountered in biology, chemistry and
physics, involving the optimal structure of folded polymeric chains. We find
that, in cases where boundary effects are not dominant, helices with a
particular pitch-radius ratio are selected. Interestingly, the same geometry is
observed in helices in naturally-occurring proteins.Comment: 8 pages, 3 composite ps figure
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