Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation

Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve >0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

Formation of Prestellar Cores via Non-Isothermal Gas Fragmentation

Sheet-like clouds are common in turbulent gas and perhaps form via collisions between turbulent gas flows. Having examined the evolution of an isothermal shocked slab in an earlier contribution, in this work we follow the evolution of a sheet-like cloud confined by (thermal) pressure and gas in it is allowed to cool. The extant purpose of this endeavour is to study the early phases of core-formation. The observed evolution of this cloud supports the conjecture that molecular clouds themselves are three-phase media (comprising viz. a stable cold and warm medium, and a third thermally unstable medium), though it appears, clouds may evolve in this manner irrespective of whether they are gravitationally bound. We report, this sheet fragments initially due to the growth of the thermal instability (TI) and some fragments are elongated, filament-like. Subsequently, relatively large fragments become gravitationally unstable and sub-fragment into smaller cores. The formation of cores appears to be a three stage process: first, growth of the TI leads to rapid fragmentation of the slab; second, relatively small fragments acquire mass via gas-accretion and/or merger and third, sufficiently massive fragments become susceptible to the gravitational instability and sub-fragment to form smaller cores. We investigate typical properties of clumps (and smaller cores) resulting from this fragmentation process. Findings of this work support the suggestion that the weak velocity field usually observed in dense clumps and smaller cores is likely seeded by the growth of dynamic instabilities. Simulations were performed using the smooth particle hydrodynamics algorithm.

Structural variations in aromatic 2 pi-electron three-membered rings of the main group elements

Structural variations of different Z pi-aromatic three-membered ring systems of main group elements, especially group 14 and 13 elements as compared to the classical description of cyclopropenyl cation has been reviewed in this article. The structures of heavier analogues as well as group 13 analogues of cyclopropenyl cation showed an emergence of dramatic structural patterns which do not conform, to the general norms of carbon chemistry. Isolobal analogies between the main group fragments have been efficiently used to explain the peculiarities observed in these three-membered ring systems.

Stability of Filaments in Star-Forming Clouds and the Formation of Prestellar Cores in Them

The exact process(es) that generate(s) dense filaments which then form prestellar cores within them is unclear. Here we study the formation of a dense filament using a relatively simple set-up of a pressure-confined, uniform-density cylinder. We examine if its propensity to form a dense filament and further, to the formation of prestellar cores along this filament, bears on the gravitational state of the initial volume of gas. We report a radial collapse leading to the formation of a dense filamentary cloud is likely when the initial volume of gas is at least critically stable (characterised by the approximate equality between the mass line-density for this volume and its maximum value). Though self-gravitating, this volume of gas, however, is not seen to be in free-fall. This post-collapse filament then fragments along its length due to the growth of a Jeans-like instability to form prestellar cores. We suggest dense filaments in typical star-forming clouds classified as gravitationally super-critical under the assumption of: (i) isothermality when in fact, they are not, and (ii) extended radial profiles as against pressure-truncated, that significantly over-estimates their mass line-density, are unlikely to experience gravitational free-fall. The radial density and temperature profile derived for this post-collapse filament is consistent with that deduced for typical filamentary clouds mapped in recent surveys of nearby star-forming regions.

Crystal landscape in the orcinol:4,4 `-bipyridine system: synthon modularity, polymorphism and transferability of multipole charge density parameters

Polymorphism in the orcinol: 4,4'-bipyridine cocrystal system is analyzed in terms of a robust convergent modular phenol...pyridine supramolecular synthon. Employing the Synthon Based Fragments Approach (SBFA) to transfer the multipole charge density parameters, it is demonstrated that the crystal landscape can be quantified in terms of intermolecular interaction energies in the five crystal forms so far isolated in this complex system. There are five crystal forms. The first has an open, divergent O-H...N based structure with alternating orcinol and bipyridine molecules. The other four polymorphs have different three-dimensional packing but all of them are similar at an interaction level, and are based on a modular O-H...N mediated supramolecular synthon that consists of two orcinol and two bipyridine molecules in a closed, convergent structure. The SBFA method, which depends on the modularity of synthons, provides good agreement between experiment and theory because it takes into account the supramolecular contribution to charge density. The existence of five crystal forms in this system shows that polymorphism in cocrystals need not be considered to be an unusual phenomenon. Studies of the crystal landscape could lead to an understanding of the kinetic pathways that control the crystallization processes, in other words the valleys in the landscape. These pathways are traditionally not considered in exercises pertaining to computational crystal structure prediction, which rather monitors the thermodynamics of the various stable forms in the system, in other words the peaks in the landscape.

Molecular Dissection of Mycobacterium tuberculosis Integration Host Factor Reveals Novel Insights into the Mode of DNA Binding and Nucleoid Compaction

The annotated whole-genome sequence of Mycobacterium tuberculosis indicated that Rv1388 (Mtihf) likely encodes a putative 20 kDa integration host factor (mIHF). However, very little is known about the functional properties of mIHF or organization of mycobacterial nucleoid. Molecular modeling of the mIHF three-dimensional structure, based on the cocrystal structure of Streptomyces coelicolor IHF-duplex DNA, a bona fide relative of mIHF, revealed the presence of Arg170, Arg171, and Arg173, which might be involved in DNA binding, and a conserved proline (P150) in the tight turn. The phenotypic sensitivity of Escherichia coli Delta ihfA and Delta ihfB strains to UV and methylmethanesulfonate could be complemented with the wild-type Mtihf, but not its alleles bearing mutations in the DNA-binding residues. Protein DNA interaction assays revealed that wild-type mIHF, but not its DNA-binding variants, bind with high affinity to fragments containing attB and attP sites and curved DNA. Strikingly, the functionally important amino acid residues of mIHF and the mechanism(s) underlying its binding to DNA, DNA bending, and site-specific recombination are fundamentally different from that of E. coli IHF alpha beta. Furthermore, we reveal novel insights into IHF-mediated DNA compaction depending on the placement of its preferred binding sites; mIHF promotes compaction of DNA into nucleoid-like or higher-order filamentous structures. We hence propose that mIHF is a distinct member of a subfamily of proteins that serve as essential cofactors in site-specific recombination and nucleoid organization and that these findings represent a significant advance in our understanding of the role(s) of nucleoid-associated proteins.

Contrasting Electronic Requirements for C-H Binding and C-H Activation in d(6) Half-Sandwich Complexes of Rhenium and Tungsten

A computational study of the interaction half-sandwich metal fragments (metal=Re/W, electron count=d(6)), containing linear nitrosyl (NO+), carbon monoxide (CO), trifluorophosphine (PF3), N-heterocyclic carbene (NHC) ligands with alkanes are conducted using density functional theory employing the hybrid meta-GGA functional (M06). Electron deficiency on the metal increases with the ligand in the order NHC < CO < PF3 < NO+. Electron-withdrawing ligands like NO+ lead to more stable alkane complexes than NHC, a strong electron donor. Energy decomposition analysis shows that stabilization is due to orbital interaction involving charge transfer from the alkane to the metal. Reactivity and dynamics of the alkane fragment are facilitated by electron donors on the metal. These results match most of the experimental results known for CO and PF3 complexes. The study suggests activation of alkane in metal complexes to be facile with strong donor ligands like NHC. (C) 2015 Wiley Periodicals, Inc.

Crustal Evolution of Kolli-Massif, Southern India

Southern India is a collage of numerous crustal fragments formed since the Archean (2500 Ma ago) and reworked several times during the geological history. A close look at these terrains provides a window to understand the crustal evolutionary processes experienced by the continental crust in the past, such as crustal growth (formation of crust through addition of new magma) and crustal reworking (modification of an already existing crust). Here we discuss the evolutionary history of such a crustal fragment from the Southern Granulite Terrain (SGT) in peninsular India, namely Kolli-massif. Geology, structural deformation through time, and the implications in crustal assembly of southern India are exponded.

Narrow escape: how ionizing photons escape from disc galaxies

In this paper we calculate the escape fraction (f(esc)) of ionizing photons from starburst galaxies. Using 2D axisymmetric hydrodynamic simulations, we study superbubbles created by overlapping supernovae in OB associations. We calculate the escape fraction of ionizing photons from the centre of the disc along different angles through the superbubble and the gas disc. After convolving with the luminosity function of OB associations, we show that the ionizing photons escape within a cone of similar to 40 degrees, consistent with observations of nearby galaxies. The evolution of the escape fraction with time shows that it falls initially as cold gas is accumulated in a dense shell. After the shell crosses a few scaleheights and fragments, the escape fraction through the polar regions rises again. The angle-averaged escape fraction cannot exceed similar to1 - cos (1 rad)] = 0.5 from geometrical considerations (using the emission cone opening angle). We calculate the dependence of the time-and angle-averaged escape fraction on the mid-plane disc gas density (in the range n(0) = 0.15-50 cm(-3)) and the disc scaleheight (between z(0) = 10 and 600 pc). We find that the escape fraction is related to the disc parameters (the mid-plane disc density and scaleheight) roughly so that f(esc)(alpha)n(0)(2)z(0)(3) (with alpha approximate to 2.2) is a constant. For discs with a given warm neutral medium temperature, massive discs have lower escape fraction than low-mass galaxies. For Milky Way ISM parameters, we find f(esc) similar to 5 per cent, and it increases to approximate to 10 per cent for a galaxy 10 times less massive. We discuss the possible effects of clumpiness of the ISM on the estimate of the escape fraction and the implications of our results for the reionization of the Universe.

DOES THE CHEMOTHERMAL INSTABILITY HAVE ANY ROLE IN THE FRAGMENTATION OF PRIMORDIAL GAS

The collapse of the primordial gas in the density regime similar to 10(8)-10(10) cm(-3) is controlled by the three-body H-2 formation process, in which the gas can cool faster than free-fall time-a condition proposed as the chemothermal instability. We investigate how the heating and cooling rates are affected during the rapid transformation of atomic to molecular hydrogen. With a detailed study of the heating and cooling balance in a 3D simulation of Pop III collapse, we follow the chemical and thermal evolution of the primordial gas in two dark matter minihalos. The inclusion of sink particles in modified Gadget-2 smoothed particle hydrodynamics code allows us to investigate the long-term evolution of the disk that fragments into several clumps. We find that the sum of all the cooling rates is less than the total heating rate after including the contribution from the compressional heating (pdV). The increasing cooling rate during the rapid increase of the molecular fraction is offset by the unavoidable heating due to gas contraction. We conclude that fragmentation occurs because H-2 cooling, the heating due to H-2 formation and compressional heating together set a density and temperature structure in the disk that favors fragmentation, not the chemothermal instability.

H2O-CH4 and H2S-CH4 complexes: a direct comparison through molecular beam experiments and ab initio calculations

New molecular beam scattering experiments have been performed to measure the total ( elastic plus inelastic) cross sections as a function of the velocity in collisions between water and hydrogen sulfide projectile molecules and the methane target. Measured data have been exploited to characterize the range and strength of the intermolecular interaction in such systems, which are of relevance as they drive the gas phase molecular dynamics and the clathrate formation. Complementary information has been obtained by rotational spectra, recorded for the hydrogen sulfide-methane complex, with a pulsed nozzle Fourier transform microwave spectrometer. Extensive ab initio calculations have been performed to rationalize all the experimental findings. The combination of experimental and theoretical information has established the ground for the understanding of the nature of the interaction and allows for its basic components to be modelled, including charge transfer, in these weakly bound systems. The intermolecular potential for H2S-CH4 is significantly less anisotropic than for H2O-CH4, although both of them have potential minima that can be characterized as `hydrogen bonded'.

Negative Cooperativity and High Affinity in Chitooligosaccharide Binding by a Mycobacterium smegmatis Protein Containing LysM and Lectin Domains

LysM domains have been recognized in bacteria and eukaryotes as carbohydrate-binding protein modules, but the mechanism of their binding to chitooligosaccharides has been underexplored. Binding of a Mycobacterium smegmatis protein containing a lectin (MSL) and one LysM domain to chitooligosaccharides has been studied using isothermal titration calorimetry and fluorescence titration that demonstrate the presence of two binding sites of nonidentical affinities per dimeric MSL-LysM molecule. The affinity of the molecule for chitooligosaccharides correlates with the length of the carbohydrate chain. Its binding to chitooligosaccharides is characterized by negative cooperativity in the interactions of the two domains. Apparently, the flexibility of the long linker that connects the LysM and MSL domains plays a facilitating role in this recognition. The LysM domain in the MSL-LysM molecule, like other bacterial domains but unlike plant LysM domains, recognizes equally well peptidoglycan fragments as well as chitin polymers. Interestingly, in the case presented here, two LysM domains are enough for binding to peptidoglycan in contrast to the three reportedly required by the LysM domains of Bacillus subtilis and Lactococcus lactis. Also, the affinity of the MSL-LysM molecule for chitooligosaccharides is higher than that of LysM-chitooligosaccharide interactions reported so far.