Abstract

Trans Hoogsteen/sugar edge (H/SE) RNA base pairs form one of the six families of RNA base pairs that utilize the 2-hydroxyl group of ribose for base pairing and play key roles in stabilizing folded RNA molecules. Here, we provide a detailed quantum chemical characterization of intrinsic structures and interaction energies of this base pair family, along with the evaluation of solvent screening effects by a continuum solvent approach. We report DFT-optimized geometries and MP2 interaction energies for all 10 crystallographically identified members of the family, for a representative set of them, using complete basis set extrapolation. For 6 of the 10 base pairs, we had to apply geometric constraints to keep the geometries relevant to RNA. We confirm that the remaining, hitherto undetected, possible members of this family do not have appropriate steric features required to establish stable base pairing in the trans H/SE fashion. The interaction patterns in the trans H/SE family are highly diverse, with gas-phase interaction energies in the range from 1 to 17 kcal/mol. Except for the C/rC and G/rG trans H/SE base pairs, the interaction energy is roughly evenly distributed between the HF and correlation components. Thus, in the trans H/SE base pairs, the relative importance of electron correlation is noticeably smaller than in the cis WC/SE or cis and trans SE/SE base pairs, but still larger than in canonical base pairs. The trans H/SE A/rG base pair is the intrinsically most stable member of this family. This base pair is also known as the sheared AG base pair and belongs to the most prominent set of RNA base pairs utilized in molecular building blocks of functional RNAs. For all trans H/SE base pairs that we identified, in addition to conventional base pairing, viable alternative structures were stabilized by amino-acceptor interactions. In the QM calculations, these amino-acceptor complexes appear to be equally as stable as those with common H-bonds, and more importantly, the switch to amino-acceptor interaction does not require any significant geometrical rearrangement of the base pairs. Such interactions are worthy of further investigations, as X-ray crystallography cannot unambiguously distinguish between conventional and amino-acceptor interactions involving the 2-hydroxyl group, formation of such interactions is usually not considered, and molecular modeling force fields do not include such interactions properly as a result of neglect of amino-group pyramidalization.

Abstract

Computed tomographic (CT) images are widely used in the diagnosis of stroke. In this paper, we present an automated method to detect and classify an abnormality into acute infarct, chronic infarct and hemorrhage at the slice level of non-contrast CT images. The proposed method consists of three main steps: image enhancement, detection of mid-line symmetry and classification of abnormal slices. A windowing operation is performed on the intensity distribution to enhance the region of interest. Domain knowledge about the anatomical structure of the skull and the brain is used to detect abnormalities in a rotation- and translation-invariant manner. A two-level classification scheme is used to detect abnormalities using features derived in the intensity and the wavelet domain. The proposed method has been evaluated on a dataset of 15 patients (347 image slices). The method gives 90% accuracy and 100% recall in detecting abnormality at patient level; and achieves an average precision of 91% and recall of 90% at the slice level.

Abstract

We solve instances of a general class of problems de- ned as follows: Preprocess a set S of possibly weighted colored geometric objects (e.g. points/orthogonal seg- ments/rectangles) in Rd, d  1 such that given a query orthogonal range q, we can report eciently for each dis- tinct color c of the points in S \q, the tuple < c;F(c) > where F(c) is a function (e.g. weighted sum, bounding box etc.) of the objects of color c in q.

Abstract

Water bodies, the aquatic systems on land, are one of the important store houses for variety of wildlife as well as nesting and breeding sites for different kind of avifauna. Currently these water bodies are under tremendous human pressure due to rapid urbanization. The lakes and reservoirs, across the country, are in varying degrees of environmental degradation due to various anthropogenic activities. In this context a study was carried out in and around the city, covering an area of about 7800 km2 to identify the impact of expanding urbanization process on water bodies of the Hyderabad city using 1989 and 2001 satellite data. The results of the study showed reduction in water bodies both in the area (19%) as well as in number. A negative change was observed in the status of water bodies towards NE and NW directions of the city. Most of the water bodies either were encroached by urban expansion or reduced in size due to eutrophication process. The expanding IT sector and developments in real estate, acted as major driving forces that converted agricultural lands into residential plots and there by exerting pressure on the nearby water bodies. The change study here provides us with vital clues towards understanding the change in water bodies’ vis-à-vis the urban needs, economic growth, and its location characteristics within a rapidly urbanization region.

Abstract

Forests are depleted drastically at higher rates to cope up the needs of increasing population. The present study was carried out to assess the impact of anthropogenic and natural disturbances (tsunami) on the vegetation of North Andaman islands using three different satellite images of different time period by visual image interpretation technique. A higher proportion of land cover and vegetation converted into agriculture, settlement, sand and water. Assessment of overall forest change from 1976 to 2005 is 117 Km 2 , with forest loss at the rate of 3.8 Km 2 / year. Simulation study for future forest scenario predicted an increase in agriculture / settlement area to be 196, 296, 392 and 492 Km 2 for the next 25, 50, 75 and 100 years, coupled with the conversion of forest areas of 131, 227, 320 and 427 Km 2 . Finally by the end of 100 years the estimated forest area of 1271 Km 2 (1999 data) reduces to 846 Km 2 if proper conservative actions are not taken.

Abstract

Macrocyclic trienes are important precursors for the synthesis of several biologically relevant molecules such as steroids. These molecules undergo (4+2) cycloaddition to form tricyclic compounds, which has four newly formed stereocenters. The stereochemistry at these four carbon centers has been shown to be largely controlled by the reaction energy barriers, and the conformational preferences of the macrocycle. Molecular dynamics (MD) simulation is a highly efficient approach for studying conformational properties of chemical molecules and biological macromolecules. MP2/6-31G* method was used to obtain potential energy surfaces corresponding to appropriate model compounds and used as the target data. The force field parameters were refined to accurately represent the target data involving all the model compounds chosen. Using the refined molecular mechanics force field, MD simulations were performed on six possible 14-membered symmetric trienes at different temperatures. We have also used replica exchange MD (RexMD) simulations with eight replicas between 300 and 370 K. The molecules were found to sample a larger conformational space in the RexMD simulation compared to the regular MD simulations. The probability distributions corresponding to the dihedral angles, and distances between the reaction centers have been analyzed. The relationship between the conformational sampling of the macrocyclic trienes vis-à-vis their reactivity will be discussed. Additionally, clustering of the structures from the MD trajectories was done to identify all unique conformations using a new approach.

Abstract

Sac7d is a protein present in Sulfolobus acidocaldarius, a hyperthermophilic archaeon, which is stable at extreme conditions. It is a chromosomal protein, which is capable of binding DNA thereby increasing its melting temperature. It was suggested to stabilize central 3 to 5 base pair steps in DNA. It binds to the minor groove of the DNA causing a kink in the helix without any sequential preference. We have used molecular dynamics (MD) simulations to study the binary complexes of Sac7d bound to DNA at 300 and 360 K. The objective is to understand the atomic detailed mechanism of the capability of Sac7d in facilitating DNA stability at higher temperature. As has been shown before, the structure of the protein is highly stable both at 300 and 360 K. The DNA duplex was found to be stable at 300 K and is similar to the X-ray crystal structure. Consistent with experiments, at least the central four base pairs of the DNA were found to be base paired during most of the simulation at 360 K. The dynamic properties of the protein in the protein-DNA complexes remained unchanged compared to when the protein is unbound. Interestingly, B- to A-form transitions occur in both the DNA molecules when bound to Sac7d, which was confirmed by sugar puckering angles, and backbone dihedral angles. Detailed examination of the protein-DNA interactions reveals that the stabilization of the DNA molecules is mostly due to the favorable interaction of the protein with the backbone of the DNA.

Abstract

Base flipping is a process by which one of the bases of the DNA swings out from its helical position to an extrahelical form. Several proteins such as methyltransferases, glycosylases and endonucleases employ this phenomenon in order to gain access to the target base for chemical modification. Even in the absence of protein, base pair opening occurs in nucleic acids in solution. X-ray crystal studies, fluorescence spectroscopy and NMR imino proton exchange experiments have been extensively employed to study the structures and dynamics involved in this fascinating event. We have employed molecular dynamics simulations to study base flipping both in presence and absence of the protein. The free energy pathways obtained using potential of mean force calculations will be presented. The base pair opening dynamics of AT and GC base pairs was investigated by calculating the equilibrium constants corresponding to the equilibrium between the base pair open and closed states, and compared with experimental data. Our calculations showed that the contribution to the overall equilibrium constants of the base pair opening is primarily from the purine bases. The methodological issues such as sufficient sampling and force field parameters will be addressed. In another study, the role of THR250 HhaI methyltransferase in base flipping will be discussed. THR250 is a highly conserved residue in methyltransferases and was proposed to be crucial for the correct placement of flipped cytosine for methylation. Previous computational studies have shown that the protein actively facilitates the base flipping process. Free energy calculations of base flipping in the presence of the wild type and T250G, T250A and T250D mutants of the protein were computed. The free energy profiles, structural changes and the energetic parameters for the base flipping process will be presented.

Abstract

Urea concentration dependent denaturation of proteins and nucleic acids has been widely used in obtaining (un)folding pathways and in calculating the free energies. Molecular dynamics simulations were performed on a 22-nt RNA hairpin in aqueous solution environment and in different concentrations (1-8M) of urea. The energetic and structural aspects of the role of urea in denaturating the RNA hairpin were investigated. In agreement with experimental studies, the RNA undergoes denaturation at higher concentrations of urea (> 6M). Surprisingly, the hairpin was observed to be more stable at lower concentrations of urea (1-2M) even compared to the RNA in aqueous environment. Various structural, energetic and solvation properties were analyzed to understand the mechanism of the interaction of urea with the hairpin. It was observed that urea does not directly facilitate the opening of the base pairs that leads to denaturation at higher concentrations. Instead, the open states of the RNA are stabilized by via hydrogen bonding interactions and stacking interactions thereby stabilizing the denatured form of the RNA.

Abstract

Let G = (V, E) be a graph and let f: V → {0, 1} be a mapping from the set of vertices to {0, 1} and for each edge (u, v) ∊ E assign the label |f(u) — f(v)|. If the number of vertices labeled with 0 and the number of vertices labeled with 1 differ by at most 1 and the number of edges labled with 0 and the number of edges labeled with 1 differ by at most 1, then f is called a cordial labeling. In this paper, we present two families of planar graphs, Pln and Plm,n defined shortly, that admit a cordial labeling. We also show that the class Plm,n admits a total product cordial labeling under certain conditions.