5,773 research outputs found
A new perspective on the analysis of helix-helix packing preferences in globular proteins
For many years it had been believed that steric compatibility of helix
interfaces could be the source of the observed preference for particular angles
between neighbouring helices as emerging from statistical analysis of protein
databanks. Several elegant models describing how side chains on helices can
interdigitate without steric clashes were able to account quite reasonably for
the observed distributions. However, it was later recognized (Bowie, 1997 and
Walther, 1998) that the ``bare'' measured angle distribution should be
corrected to avoid statistical bias. Disappointingly, the rescaled
distributions dramatically lost their similarity with theoretical predictions
casting many doubts on the validity of the geometrical assumptions and models.
In this report we elucidate a few points concerning the proper choice of the
random reference distribution. In particular we show the existence of crucial
corrections due to the correct implementation of the approach used to
discriminate whether two helices are in contact or not and to measure their
relative orientations. By using this new rescaling, the ``true'' packing angle
preferences are well described, even more than with the original ``bare''
distribution, by regular packing models.Comment: 23 pages, 5 figure
Simple solvation potential for coarse-grained models of proteins
We formulate a simple solvation potential based on a coarsed-grain
representation of amino acids with two spheres modeling the atom and
an effective side-chain centroid. The potential relies on a new method for
estimating the buried area of residues, based on counting the effective number
of burying neighbours in a suitable way. This latter quantity shows a good
correlation with the buried area of residues computed from all atom
crystallographic structures. We check the discriminatory power of the solvation
potential alone to identify the native fold of a protein from a set of decoys
and show the potential to be considerably selective.Comment: 18 pages, 8 tables, 3 figure
Phase diagram of force-induced DNA unzipping in exactly solvable models
The mechanical separation of the double helical DNA structure induced by
forces pulling apart the two DNA strands (``unzipping'') has been the subject
of recent experiments. Analytical results are obtained within various models of
interacting pairs of directed walks in the (1,1,...,1) direction on the
hypercubic lattice, and the phase diagram in the force-temperature plane is
studied for a variety of cases. The scaling behaviour is determined at both the
unzipping and the melting transition. We confirm the existence of a cold
denaturation transition recently observed in numerical simulations: for a
finite range of forces the system gets unzipped by {\it decreasing} the
temperature. The existence of this transition is rigorously established for
generic lattice and continuum space models.Comment: 19 pages, 5 eps figures; revised version with minor changes,
presentation simplified in the text with details in appendix. Accepted for
publication in Phys. Rev.
Swollen-Collapsed Transition in Random Hetero-Polymers
A lattice model of a hetero-polymer with random hydrophilic-hydrophobic
charges interacting with the solvent is introduced, whose continnuum
counterpart has been proposed by T. Garel, L. Leibler and H. Orland {J. Phys.
II France 4, 2139 (1994)]. The transfer matrix technique is used to study
various constrained annealed systems which approximate at various degrees of
accuracy the original quenched model. For highly hydrophobic chains an ordinary
-point transition is found from a high temperature swollen phase to a
low temperature compact phase. Depending on the type of constrained averages,
at very low temperatures a swollen phase or a coexistence between compact and
swollen phases are found. The results are carefully compared with the
corresponding ones obtained in the continuum limit, and various improvements in
the original calculations are discussed.Comment: 13 pages, 8 figures; revised version with minor changes, accepted for
publication in European Physical Journal
Heteropolymers in a Solvent at an Interface
Exact bounds are obtained for the quenched free energy of a polymer with
random hydrophobicities in the presence of an interface separating a polar from
a non polar solvent. The polymer may be ideal or have steric self-interactions.
The bounds allow to prove that a ``neutral'' random polymer is localized near
the interface at any temperature, whereas a ``non-neutral'' chain is shown to
undergo a delocalization transition at a finite temperature. These results are
valid for a quite general a priori probability distribution for both
independent and correlated hydrophobic charges. As a particular case we
consider random AB-copolymers and confirm recent numerical studies.Comment: 4 pages, no figure
Geometry of compact tubes and protein structures
Proteins form a very important class of polymers. In spite of major advances
in the understanding of polymer science, the protein problem has remained
largely unsolved. Here, we show that a polymer chain viewed as a tube not only
captures the well-known characteristics of polymers and their phases but also
provides a natural explanation for many of the key features of protein
behavior. There are two natural length scales associated with a tube subject to
compaction -- the thickness of the tube and the range of the attractive
interactions. For short tubes, when these length scales become comparable, one
obtains marginally compact structures, which are relatively few in number
compared to those in the generic compact phase of polymers. The motifs
associated with the structures in this new phase include helices, hairpins and
sheets. We suggest that Nature has selected this phase for the structures of
proteins because of its many advantages including the few candidate strucures,
the ability to squeeze the water out from the hydrophobic core and the
flexibility and versatility associated with being marginally compact. Our
results provide a framework for understanding the common features of all
proteins.Comment: 15 pages, 3 eps figure
Non-alcoholic fatty liver disease: relationship with cardiovascular risk markers and clinical endpoints
Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the
disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy.
NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence
of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery
calcification score.
There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change,with close attention to known cardiovascular risk factors
Variety, Competition, and Population in Economic Growth : Theory and Empirics
We provide aggregate macroeconomic evidence on how, in the long-run, a diverse degree of complexity in production may affect not only the rate of economic growth, but also the correlation between the latter, population growth and the monopolistic (intermediate) markups. For a sample of OECD countries, we find that the impact of population change on economic growth is slightly positive. According to our the- oretical model, this implies that the losses due to more complexity in production are lower than the corresponding specialization gains. Using a Finite Mixture Model, we also classify the countries in the sample and verify for each cluster the impact that the population growth rate and the intermediate sector\u2019s markups exert on the 5-year average real GDP growth rate
Variety, Competition, and Population in Economic Growth: Theory and Empirics
We provide aggregate macroeconomic evidence on how, in the long-run, a diverse degree of production-complexity may affect not only the rate of economic growth, but also the correlation between the latter, population growth and the monopolistic (intermediate) markups. For a sample of OECD economies, we find that the losses due to more complexity in production are lower than the corresponding specialization gains. According to our theoretical model, this implies that the impact of population change on economic growth is slightly positive. Using a Finite Mixture Model, we also classify the countries in the sample and verify for each cluster the impact that the population growth rate and the intermediate sector's markups exert on the 5-year average real GDP growth rate
Key interaction patterns in proteins revealed by cluster expansion of the partition function
The native conformation of structured proteins is stabilized by a complex
network of interactions. We analyzed the elementary patterns that constitute
such network and ranked them according to their importance in shaping protein
sequence design. To achieve this goal, we employed a cluster expansion of the
partition function in the space of sequences and evaluated numerically the
statistical importance of each cluster. An important feature of this procedure
is that it is applied to a dense, finite system. We found that patterns that
contribute most to the partition function are cycles with even numbers of
nodes, while cliques are typically detrimental. Each cluster also gives a
contribute to the sequence entropy, which is a measure of the evolutionary
designability of a fold. We compared the entropies associated with different
interaction patterns to their abundances in the native structures of real
proteins
- …