1,232 research outputs found
Exploiting Homology Information in Nontemplate Based Prediction of Protein Structures
In this paper we describe a novel strategy for exploring the conformational space of proteins and show that this leads to better models for proteins the structure of which is not amenable to template based methods. Our strategy is based on the assumption that the energy global minimum of homologous proteins must correspond to similar conformations, while the precise profiles of their energy landscape, and consequently the positions of the local minima, are likely to be different. In line with this hypothesis, we apply a replica exchange Monte Carlo simulation protocol that, rather than using different parameters for each parallel simulation, uses the sequences of homologous proteins. We show that our results are competitive with respect to alternative methods, including those producing the best model for each of the analyzed targets in the CASP10 (10th Critical Assessment of techniques for protein Structure Prediction) experiment free modeling category
Introduction to protein folding for physicists
The prediction of the three-dimensional native structure of proteins from the
knowledge of their amino acid sequence, known as the protein folding problem,
is one of the most important yet unsolved issues of modern science. Since the
conformational behaviour of flexible molecules is nothing more than a complex
physical problem, increasingly more physicists are moving into the study of
protein systems, bringing with them powerful mathematical and computational
tools, as well as the sharp intuition and deep images inherent to the physics
discipline. This work attempts to facilitate the first steps of such a
transition. In order to achieve this goal, we provide an exhaustive account of
the reasons underlying the protein folding problem enormous relevance and
summarize the present-day status of the methods aimed to solving it. We also
provide an introduction to the particular structure of these biological
heteropolymers, and we physically define the problem stating the assumptions
behind this (commonly implicit) definition. Finally, we review the 'special
flavor' of statistical mechanics that is typically used to study the
astronomically large phase spaces of macromolecules. Throughout the whole work,
much material that is found scattered in the literature has been put together
here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to
arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co
Designability of alpha-helical Proteins
A typical protein structure is a compact packing of connected alpha-helices
and/or beta-strands. We have developed a method for generating the ensemble of
compact structures a given set of helices and strands can form. The method is
tested on structures composed of four alpha-helices connected by short turns.
All such natural four-helix bundles that are connected by short turns seen in
nature are reproduced to closer than 3.6 Angstroms per residue within the
ensemble. Since structures with no natural counterpart may be targets for ab
initio structure design, the designability of each structure in the ensemble --
defined as the number of sequences with that structure as their lowest energy
state -- is evaluated using a hydrophobic energy. For the case of four
alpha-helices, a small set of highly designable structures emerges, most of
which have an analog among the known four-helix fold families, however several
novel packings and topologies are identified.Comment: 21 pages, 6 figures, to appear in PNA
Unfolding Rates for the Diffusion-Collision Model
In the diffusion-collision model, the unfolding rates are given by the
likelihood of secondary structural cluster dissociation. In this work, we
introduce an unfolding rate calculation for proteins whose secondary structural
elements are -helices, modeled from thermal escape over a barrier which
arises from the free energy in buried hydrophobic residues. Our results are in
good agreement with currently accepted values for the attempt rate.Comment: Shorter version of cond-mat/0011024 accepted for publication in PR
The Origin of the Designability of Protein Structures
We examined what determines the designability of 2-letter codes (H and P)
lattice proteins from three points of view. First, whether the native structure
is searched within all possible structures or within maximally compact
structures. Second, whether the structure of the used lattice is bipartite or
not. Third, the effect of the length of the chain, namely, the number of
monomers on the chain. We found that the bipartiteness of the lattice structure
is not a main factor which determines the designability. Our results suggest
that highly designable structures will be found when the length of the chain is
sufficiently long to make the hydrophobic core consisting of enough number of
monomers.Comment: 17 pages, 2 figure
From coordination to stochastic models of QoS
Reo is a channel-based coordination model whose operational semantics is given by Constraint Automata (CA). Quantitative Constraint Automat
Compositionality Results for Quantitative Information Flow
International audienceIn the min-entropy approach to quantitative information flow, the leakage is defined in terms of a minimization problem, which, in case of large systems, can be computationally rather heavy. The same happens for the recently proposed generalization called g-vulnerability. In this paper we study the case in which the channel associated to the system can be decomposed into simpler channels, which typically happens when the observables consist of several components. Our main contribution is the derivation of bounds on the g-leakage of the whole system in terms of the g-leakage of its components
Swelfe: a detector of internal repeats in sequences and structures
Summary: Intragenic duplications of genetic material have important biological roles because of their protein sequence and structural consequences. We developed Swelfe to find internal repeats at three levels. Swelfe quickly identifies statistically significant internal repeats in DNA and amino acid sequences and in 3D structures using dynamic programming. The associated web server also shows the relationships between repeats at each level and facilitates visualization of the results
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
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