321 research outputs found
Resolution exchange simulation
We extend replica exchange simulation in two ways, and apply our approaches
to biomolecules. The first generalization permits exchange simulation between
models of differing resolution -- i.e., between detailed and coarse-grained
models. Such ``resolution exchange'' can be applied to molecular systems or
spin systems. The second extension is to ``pseudo-exchange'' simulations, which
require little CPU usage for most levels of the exchange ladder and also
substantially reduces the need for overlap between levels. Pseudo exchanges can
be used in either replica or resolution exchange simulations. We perform
efficient, converged simulations of a 50-atom peptide to illustrate the new
approaches.Comment: revised manuscript: 4.2 pages, 3 figure
Medium effects on the selection of sequences folding into stable proteins in a simple model
We study the medium effects on the selection of sequences in protein folding
by taking account of the surface potential in HP-model. Our analysis on the
proportion of H and P monomers in the sequences gives a direct interpretation
that the lowly designable structures possess small average gap. The numerical
calculation by means of our model exhibits that the surface potential enhances
the average gap of highly designable structures. It also shows that a most
stable structure may be no longer the most stable one if the medium parameters
changed.Comment: 4 pages, 4 figure
Folding dynamics of the helical structures in a minimal model
The folding of a polypeptide is an example of the cooperative effects of the
amino-acid residues. Of recent interest is how a secondary structure, such as a
helix, spontaneously forms during the collapse of a peptide from an initial
denatured state. The Monte Carlo implementation of a recent helix-forming model
enables us to study the entire folding process dynamically.
As shown by the computer simulations, the foldability and helical propagation
are both strongly correlated to the nucleation properties of the sequence.Comment: 3 figures Submitted to Europhys Lette
Characteristic Temperatures of Folding of a Small Peptide
We perform a generalized-ensemble simulation of a small peptide taking the
interactions among all atoms into account. From this simulation we obtain
thermodynamic quantities over a wide range of temperatures. In particular, we
show that the folding of a small peptide is a multi-stage process associated
with two characteristic temperatures, the collapse temperature T_{\theta} and
the folding temperature T_f. Our results give supporting evidence for the
energy landscape picture and funnel concept. These ideas were previously
developed in the context of studies of simplified protein models, and here for
the first time checked in an all-atom Monte Carlo simulation.Comment: Latex, 6 Figure
A network model to investigate structural and electrical properties of proteins
One of the main trend in to date research and development is the
miniaturization of electronic devices. In this perspective, integrated
nanodevices based on proteins or biomolecules are attracting a major interest.
In fact, it has been shown that proteins like bacteriorhodopsin and azurin,
manifest electrical properties which are promising for the development of
active components in the field of molecular electronics. Here we focus on two
relevant kinds of proteins: The bovine rhodopsin, prototype of GPCR protein,
and the enzyme acetylcholinesterase (AChE), whose inhibition is one of the most
qualified treatments of Alzheimer disease. Both these proteins exert their
functioning starting with a conformational change of their native structure.
Our guess is that such a change should be accompanied with a detectable
variation of their electrical properties. To investigate this conjecture, we
present an impedance network model of proteins, able to estimate the different
electrical response associated with the different configurations. The model
resolution of the electrical response is found able to monitor the structure
and the conformational change of the given protein. In this respect, rhodopsin
exhibits a better differential response than AChE. This result gives room to
different interpretations of the degree of conformational change and in
particular supports a recent hypothesis on the existence of a mixed state
already in the native configuration of the protein.Comment: 25 pages, 12 figure
Folding of small proteins: A matter of geometry?
We review some of our recent results obtained within the scope of simple
lattice models and Monte Carlo simulations that illustrate the role of native
geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic
Additional Resection of the Pancreas Body Prevents Postoperative Pancreas Fistula in Patients with Portal Annular Pancreas Who Undergo Pancreaticoduodenectomy
Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein. Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction
Discrete molecular dynamics simulations of peptide aggregation
We study the aggregation of peptides using the discrete molecular dynamics
simulations. At temperatures above the alpha-helix melting temperature of a
single peptide, the model peptides aggregate into a multi-layer parallel
beta-sheet structure. This structure has an inter-strand distance of 0.48 nm
and an inter-sheet distance of 1.0 nm, which agree with experimental
observations. In this model, the hydrogen bond interactions give rise to the
inter-strand spacing in beta-sheets, while the Go interactions among side
chains make beta-strands parallel to each other and allow beta-sheets to pack
into layers. The aggregates also contain free edges which may allow for further
aggregation of model peptides to form elongated fibrils.Comment: 15 pages, 8 figure
Entropic Barriers, Frustration and Order: Basic Ingredients in Protein Folding
We solve a model that takes into account entropic barriers, frustration, and
the organization of a protein-like molecule. For a chain of size , there is
an effective folding transition to an ordered structure. Without frustration,
this state is reached in a time that scales as , with
. This scaling is limited by the amount of frustration which
leads to the dynamical selectivity of proteins: foldable proteins are limited
to monomers; and they are stable in {\it one} range of temperatures,
independent of size and structure. These predictions explain generic properties
of {\it in vivo} proteins.Comment: 4 pages, 4 Figures appended as postscript fil
Serum and Salivary IgE, IgA, and IgG4 Antibodies to Dermatophagoides pteronyssinus and Its Major Allergens, Der p1 and Der p2, in Allergic and Nonallergic Children
Allergic rhinitis (AR) is a public health problem with high prevalence worldwide. We evaluated levels of specific IgE, IgA, and IgG4 antibodies to the Dermatophagoides pteronyssinus (Dpt) house dust mite and to its major allergens (Der p1 and Der p2) in serum and saliva samples from allergic and nonallergic children. A total of 86 children were analyzed, from which 72 had AR and 14 were nonallergic healthy children. Serum IgE and serum/salivary IgG4 levels to Dpt, Der p1, and Der p2 were higher in allergic children whereas serum/salivary IgA levels to all allergens were higher in nonallergic children. IgE levels positively correlated with IgG4 and IgA to all allergens in allergic children, while IgA levels negatively correlated with IgG4 to Dpt and Der p1 in nonallergic children. In conclusion, mite-specific IgA antibodies predominate in the serum and saliva of nonallergic children whereas mite-specific IgE and IgG4 are prevalent in allergic children. The presence of specific IgA appears to have a key role for the healthy immune response to mucosal allergens. Also, specific IgA measurements in serum and/or saliva may be useful for monitoring activation of tolerance-inducing mechanisms during allergen specific immunotherapeutic procedures, especially sublingual immunotherapy
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