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 $C_\alpha$ 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 $\theta$-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