252 research outputs found
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
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
Successful Treatment for Hepatic Encephalopathy Aggravated by Portal Vein Thrombosis with Balloon-Occluded Retrograde Transvenous Obliteration
This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels
Magnetism, FeS colloids, and Origins of Life
A number of features of living systems: reversible interactions and weak
bonds underlying motor-dynamics; gel-sol transitions; cellular connected
fractal organization; asymmetry in interactions and organization; quantum
coherent phenomena; to name some, can have a natural accounting via
interactions, which we therefore seek to incorporate by expanding the horizons
of `chemistry-only' approaches to the origins of life. It is suggested that the
magnetic 'face' of the minerals from the inorganic world, recognized to have
played a pivotal role in initiating Life, may throw light on some of these
issues. A magnetic environment in the form of rocks in the Hadean Ocean could
have enabled the accretion and therefore an ordered confinement of
super-paramagnetic colloids within a structured phase. A moderate H-field can
help magnetic nano-particles to not only overcome thermal fluctuations but also
harness them. Such controlled dynamics brings in the possibility of accessing
quantum effects, which together with frustrations in magnetic ordering and
hysteresis (a natural mechanism for a primitive memory) could throw light on
the birth of biological information which, as Abel argues, requires a
combination of order and complexity. This scenario gains strength from
observations of scale-free framboidal forms of the greigite mineral, with a
magnetic basis of assembly. And greigite's metabolic potential plays a key role
in the mound scenario of Russell and coworkers-an expansion of which is
suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed
Krishnaswami Alladi, Springer 201
The N-Myc Down Regulated Gene1 (NDRG1) Is a Rab4a Effector Involved in Vesicular Recycling of E-Cadherin
Cell to cell adhesion is mediated by adhesion molecules present on the cell surface. Downregulation of molecules that form the adhesion complex is a characteristic of metastatic cancer cells. Downregulation of the N-myc down regulated gene1 (NDRG1) increases prostate and breast metastasis. The exact function of NDRG1 is not known. Here by using live cell confocal microscopy and in vitro reconstitution, we report that NDRG1 is involved in recycling the adhesion molecule E-cadherin thereby stabilizing it. Evidence is provided that NDRG1 recruits on recycling endosomes in the Trans Golgi network by binding to phosphotidylinositol 4-phosphate and interacts with membrane bound Rab4aGTPase. NDRG1 specifically interacts with constitutively active Rab4aQ67L mutant protein and not with GDP-bound Rab4aS22N mutant proving NDRG1 as a novel Rab4a effector. Transferrin recycling experiments reveals NDRG1 colocalizes with transferrin during the recycling phase. NDRG1 alters the kinetics of transferrin recycling in cells. NDRG1 knockdown cells show a delay in recycling transferrin, conversely NDRG1 overexpressing cells reveal an increase in rate of transferrin recycling. This novel finding of NDRG1 as a recycling protein involved with recycling of E-cadherin will aid in understanding NDRG1 role as a metastasis suppressor protein
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