2,731 research outputs found
Teaching computers to fold proteins
A new general algorithm for optimization of potential functions for protein
folding is introduced. It is based upon gradient optimization of the
thermodynamic stability of native folds of a training set of proteins with
known structure. The iterative update rule contains two thermodynamic averages
which are estimated by (generalized ensemble) Monte Carlo. We test the learning
algorithm on a Lennard-Jones (LJ) force field with a torsional angle
degrees-of-freedom and a single-atom side-chain. In a test with 24 peptides of
known structure, none folded correctly with the initial potential functions,
but two-thirds came within 3{\AA} to their native fold after optimizing the
potential functions.Comment: 4 pages, 3 figure
A model for the accidental catalysis of protein unfolding in vivo
Activated processes such as protein unfolding are highly sensitive to
heterogeneity in the environment. We study a highly simplified model of a
protein in a random heterogeneous environment, a model of the in vivo
environment. It is found that if the heterogeneity is sufficiently large the
total rate of the process is essentially a random variable; this may be the
cause of the species-to-species variability in the rate of prion protein
conversion found by Deleault et al. [Nature, 425 (2003) 717].Comment: 5 pages, 2 figure
Local softness, softness dipole and polarizabilities of functional groups: application to the side chains of the twenty amino acids
The values of molecular polarizabilities and softnesses of the twenty amino
acids were computed ab initio (MP2). By using the iterative Hirshfeld scheme to
partition the molecular electronic properties, we demonstrate that the values
of the softness of the side chain of the twenty amino acid are clustered in
groups reflecting their biochemical classification, namely: aliphatic, basic,
acidic, sulfur containing, and aromatic amino acids . The present findings are
in agreement with previous results using different approximations and
partitioning schemes [P. Senet and F. Aparicio, J. Chem. Phys. 126,145105
(2007)]. In addition, we show that the polarizability of the side chain of an
amino acid depends mainly on its number of electrons (reflecting its size) and
consequently cannot be used to cluster the amino acids in different biochemical
groups, in contrast to the local softness. Our results also demonstrate that
the global softness is not simply proportional to the global polarizability in
disagreement with the intuition that "a softer moiety is also more
polarizable". Amino acids with the same softness may have a polarizability
differing by a factor as large as 1.7. This discrepancy can be understood from
first principles as we show that the molecular polarizability depends on a
"softness dipole vector" and not simply on the global softness
Proteins and polymers
Proteins, chain molecules of amino acids, behave in ways which are similar to
each other yet quite distinct from standard compact polymers. We demonstrate
that the Flory theorem, derived for polymer melts, holds for compact protein
native state structures and is not incompatible with the existence of
structured building blocks such as -helices and -strands. We
present a discussion on how the notion of the thickness of a polymer chain,
besides being useful in describing a chain molecule in the continuum limit,
plays a vital role in interpolating between conventional polymer physics and
the phase of matter associated with protein structures.Comment: 7 pages, 6 figure
Design of Copolymeric Materials
We devise a method for designing materials that will have some desired
structural characteristics. We apply it to multiblock copolymers that have two
different types of monomers, A and B. We show how to determine what sequence of
A's and B's should be synthesised in order to give a particular structure and
morphology. %For example in a melt of such %polymers, one may wish to engineer
a body-centered %cubic structure. Using this method in conjunction with the
theory of microphase separation developed by Leibler, we show it is possible to
efficiently search for a desired morphology. The method is quite general and
can be extended to design isolated heteropolymers, such as proteins, with
desired structural characteristics. We show that by making certain
approximations to the exact algorithm, a method recently proposed by
Shakhnovich and Gutin is obtained. The problems with this method are discussed
and we propose an improved approximate algorithm that is computationally
efficient.Comment: 15 pages latex 2.09 and psfig, 1 postscript figure
Response of the Brazilian gravitational wave detector to signals from a black hole ringdown
It is assumed that a black hole can be disturbed in such a way that a
ringdown gravitational wave would be generated. This ringdown waveform is well
understood and is modelled as an exponentially damped sinusoid. In this work we
use this kind of waveform to study the performance of the SCHENBERG
gravitational wave detector. This first realistic simulation will help us to
develop strategies for the signal analysis of this Brazilian detector. We
calculated the signal-to-noise ratio as a function of frequency for the
simulated signals and obtained results that show that SCHENBERG is expected to
be sensitive enough to detect this kind of signal up to a distance of .Comment: 5 pages, 4 figures, Amaldi 5 Conference Proceedings contribution.
Submitted to Class. Quantum Gra
A refined hydrogen bond potential for flexible protein models
One of the major disadvantages of coarse-grained hydrogen bond potentials, for their use in protein folding simulations, is the appearance of abnormal structures when these potentials are used in flexible chain models, and no other geometrical restrictions or energetic contributions are defined into the system.We have efficiently overcome this problem, for chains of adequate size in a relevant temperature range, with a refined coarse-grained hydrogen bond potential. With it, we have been able to obtain nativelike alpha-helices and beta-sheets in peptidic systems, and successfully reproduced the competition between the populations of these secondary structure elements by the effect of temperature and concentration changes. In this manuscript we detail the design of the interaction potential and thoroughly examine its applicability in energetic and structural terms, considering factors such as chain length, concentration, and temperature
Lattice model for cold and warm swelling of polymers in water
We define a lattice model for the interaction of a polymer with water. We
solve the model in a suitable approximation. In the case of a non-polar
homopolymer, for reasonable values of the parameters, the polymer is found in a
non-compact conformation at low temperature; as the temperature grows, there is
a sharp transition towards a compact state, then, at higher temperatures, the
polymer swells again. This behaviour closely reminds that of proteins, that are
unfolded at both low and high temperatures.Comment: REVTeX, 5 pages, 2 EPS figure
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
Parallelization of Markov chain generation and its application to the multicanonical method
We develop a simple algorithm to parallelize generation processes of Markov
chains. In this algorithm, multiple Markov chains are generated in parallel and
jointed together to make a longer Markov chain. The joints between the
constituent Markov chains are processed using the detailed balance. We apply
the parallelization algorithm to multicanonical calculations of the
two-dimensional Ising model and demonstrate accurate estimation of
multicanonical weights.Comment: 15 pages, 5 figures, uses elsart.cl
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