Does changing the pulling direction give better insight into biomolecules?

Single molecule manipulation techniques reveal that the mechanical resistance of a protein depends on the direction of the applied force. Using a lattice model of polymers, we show that changing the pulling direction leads to different phase diagrams. The simple model proposed here indicates that in one case the system undergoes a transition akin to the unzipping of a $\beta$ sheet, while in the other case the transition is of a shearing (slippage) nature. Our results are qualitatively similar to experimental results. This demonstrates the importance of varying the pulling direction since this may yield enhanced insights into the molecular interactions responsible for the stability of biomolecules.Comment: RevTeX v4, 10 pages with 6 eps figure

Low Degree Metabolites Explain Essential Reactions and Enhance Modularity in Biological Networks

Recently there has been a lot of interest in identifying modules at the level of genetic and metabolic networks of organisms, as well as in identifying single genes and reactions that are essential for the organism. A goal of computational and systems biology is to go beyond identification towards an explanation of specific modules and essential genes and reactions in terms of specific structural or evolutionary constraints. In the metabolic networks of E. coli, S. cerevisiae and S. aureus, we identified metabolites with a low degree of connectivity, particularly those that are produced and/or consumed in just a single reaction. Using FBA we also determined reactions essential for growth in these metabolic networks. We find that most reactions identified as essential in these networks turn out to be those involving the production or consumption of low degree metabolites. Applying graph theoretic methods to these metabolic networks, we identified connected clusters of these low degree metabolites. The genes involved in several operons in E. coli are correctly predicted as those of enzymes catalyzing the reactions of these clusters. We independently identified clusters of reactions whose fluxes are perfectly correlated. We find that the composition of the latter `functional clusters' is also largely explained in terms of clusters of low degree metabolites in each of these organisms. Our findings mean that most metabolic reactions that are essential can be tagged by one or more low degree metabolites. Those reactions are essential because they are the only ways of producing or consuming their respective tagged metabolites. Furthermore, reactions whose fluxes are strongly correlated can be thought of as `glued together' by these low degree metabolites.Comment: 12 pages main text with 2 figures and 2 tables. 16 pages of Supplementary material. Revised version has title changed and contains study of 3 organisms instead of 1 earlie

Flux-based classification of reactions reveals a functional bow-tie organization of complex metabolic networks

Unraveling the structure of complex biological networks and relating it to their functional role is an important task in systems biology. Here we attempt to characterize the functional organization of the large-scale metabolic networks of three microorganisms. We apply flux balance analysis to study the optimal growth states of these organisms in different environments. By investigating the differential usage of reactions across flux patterns for different environments, we observe a striking bimodal distribution in the activity of reactions. Motivated by this, we propose a simple algorithm to decompose the metabolic network into three sub-networks. It turns out that our reaction classifier which is blind to the biochemical role of pathways leads to three functionally relevant sub-networks that correspond to input, output and intermediate parts of the metabolic network with distinct structural characteristics. Our decomposition method unveils a functional bow-tie organization of metabolic networks that is different from the bow-tie structure determined by graph-theoretic methods that do not incorporate functionality.Comment: 11 pages, 6 figures, 1 tabl

Stretching of a single-stranded DNA: Evidence for structural transition

Recent experiments have shown that the force-extension (F-x) curve for single-stranded DNA (ssDNA) consisting only of adenine [poly(dA)] is significantly different from thymine [poly(dT)]. Here, we show that the base stacking interaction is not sufficient to describe the F-x curves as seen in the experiments. A reduction in the reaction co-ordinate arising from the formation of helix at low forces and an increase in the distance between consecutive phosphates of unstacked bases in the stretched state at high force in the proposed model, qualitatively reproduces the experimentally observed features. The multi-step plateau in the F-x curve is a signature of structural change in ssDNA.Comment: 10 pages, 4 figure

Force induced triple point for interacting polymers

We show the existence of a force induced triple point in an interacting polymer problem that allows two zero-force thermal phase transitions. The phase diagrams for three different models of mutually attracting but self avoiding polymers are presented. One of these models has an intermediate phase and it shows a triple point but not the others. A general phase diagram with multicritical points in an extended parameter space is also discussed.Comment: 4 pages, 8 figures, revtex

A study to know the serum total testosterone levels in type II diabetes mellitus male patients from North India

Background: Diabetes mellitus is major public health issue facing the world in present century and the prevalence of type 2 diabetes is increasing explosively.  There are various diabetes related complications, one of which is low testosterone levels in men. This study was designed to estimate the serum testosterone level in male patients of type 2 diabetes mellitus.Methods: The patients of type -2 diabetes mellitus were picked up from out-patient and in-patients section of the hospital at random.Results: Seventy male  patients with type 2 diabetes mellitus were enrolled during the study period. The mean age of study population was 56.36±10.26 years (range 36-70), while that of control group patients was found to be 39.80±7.92years. Family history of diabetes was present in 14 (22.2%) patients. The mean HbA1c in study group was 8.83±1.95 %, which was significantly higher as compared to control group with HbA1c 4.82±0.40 %. Among study group, lower serum total testosterone level was observed in 85.7 % cases and normal level in 14.3 % cases. Among control group, lower serum total testosterone level was observed in 6.7 % cases and normal level in 93.3 % cases.Conclusions: The present study highlighted that significant difference in serum total testosterone level has been observed between cases and control groups (X2 =55.7, P=0.0001)

Effects of Eye-phase in DNA unzipping

The onset of an "eye-phase" and its role during the DNA unzipping is studied when a force is applied to the interior of the chain. The directionality of the hydrogen bond introduced here shows oscillations in force-extension curve similar to a "saw-tooth" kind of oscillations seen in the protein unfolding experiments. The effects of intermediates (hairpins) and stacking energies on the melting profile have also been discussed.Comment: RevTeX v4, 9 pages with 7 eps figure