Abstract

Peptides incorporating 5 membered rings such as furan and tetrahydrofuran (THF) adopt secondary folding patterns and thus mimic natural peptides. The preferred conformation of linear and cyclized peptides incorporating sugar amino acids depends on the stereochemistry of at the chiral center. Control of stereochemistry of THF amino acid (TAA) in the structure of the linear tripeptide Boc-TAA-Leu-Val-OMe containing (2R,5S)-cis TAA, (2S,5R)-cis TAA, (2R,5R)-trans TAA and (2S,5S)-trans TAA is investigated using structural parameters and energetics data obtained from density functional theory (DFT) based calculations at B3LYP/6-31G(d,p) level of theory. We found that the conformations associated with -, - turn structures are stabilized by intramolecular hydrogen bonding interactions. Kinetic control of reactions leading to intra and inter molecular cyclization of tripeptide TAA-Gly-Gly containing (2S,5R)-cis TAA and (2S,5S)-trans TAA is studied at the same level of theory in gas phase[1]. We observe that kinetic control favors cyclodimerization instead of intramolecular cyclization. Theoretical study of reactions leading to linear and cyclic trimerization of backbone altered -peptide, i. e., amino ethyl furan carboxylic acid (AEFC) at the same level of theory have revealed the role of stereochemistry at C position of AEFC in the preferential formation of asymmetric RRS cyclic tripeptide formed by R-, R- and S- stereo isomers of AEFC.

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

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

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

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

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

Riboswitches are structural cis-acting genetic regulatory elements in 5' UTRs of mRNAs, consisting of an aptamer domain which regulates the behavior of an expression platform in response to its recognition of, and binding to, specific ligands. While our understanding of the ligand-bound structure of the aptamer domain of adenine riboswitches is, based on crystal structure X-Ray data and is well characterized, understanding of the structure and dynamics of the ligand free aptamer is limited to indirect inferences from physico-chemical probing experiments. Here we report results of 15ns long explicit-solvent molecular dynamics simulations of the add A-riboswitch crystal structure (1Y26), both in the adenine bound (CLOSED) state and in the adenine free (OPEN) state. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), dynamic cross correlation (DCC) and backbone torsion angle analyses carried out on the two trajectories; and solvent accessible surface area (SASA) analysis of the two average structures, are benchmarked against available experimental data and are shown to constitute the basis for obtaining reliable insights into the molecular level details of the binding and switching mechanism. Our analysis reveals the interaction network responsible for, and conformational changes associated with, the communication between the binding pocket and the expression platform. It further highlights the significance of a, hither to unreported, non canonical W:H trans base pairing between A73 and A24, in the OPEN state, and also helps us to propose a possibly crucial role of U51 in the context of ligand binding and ligand discrimination.

Abstract

Schistosoma mansoni, a trematode parasite, which causes schistosomiasis and affects more than 200 million people worldwide, lives in an aerobic environment and therefore needs an effective redox mechanism for surviving reactive oxygen species from its host. Although, the host has two different redox systems: glutaredoxin and thioredoxin , the parasite has only one unique multifunctional enzyme, thioredoxin glutathione reductase (TGR) involving a fusion of two proteins, glutaredoxin (Grx) and thioredoxin reductase (TR), for performing all the redox activities. This dependence of S. mansoni on a single protein, TGR, for its protection from oxidative stress, makes it a promising drug target. Here, we describe a suitably validated, homology model for S. mansoni TGR (SmTGR), developed using both TR and Grx templates, functionally complete in the dimeric form with cofactors NADP(H) and FAD. Comparative analysis of substrate and inhibitor binding pockets of our model with crystal structures of parent TR as well as with that of glutathione reductase (GR), which is an essential component of the Grx system, appears to provide greater insight into the functioning of TGR. This also augments recent observations reported on the basis of X-ray structure data on SmTGR monomer lacking the C-terminal selenocysteine tail

Abstract

Graph theoretic concepts have been applied to the dynamic cross-correlation data obtained from MD simulation of adenine riboswitch, in absence and presence of adenine. Our hybrid approach combines community detection algorithms that support edge weights and cliques. The effect of variations in the values of nearest neighbors (NN) and correlation coefficient threshold (T) in the community detection algorithm have been applied to identify and filter out coincidental correlations between rogue nodes. Our results have identified the correlations within the structural regions of the molecule, which provide strong clues regarding the functionality and stability of the molecule in absence and presence of adenine. Our results show that a prior application of our algorithm applied to the simulation data of biomolecules in automated fashion can provide strong leads for hypothesis formulation and subsequent hypothesis-driven manual investigation.

Abstract

Schistosoma mansoni, a trematode parasite, which causes schistosomiasis and affects more than 200 million people worldwide, lives in an aerobic environment and therefore needs an effective redox mechanism for surviving reactive oxygen species from its host. Although, the host has two different redox systems: glutaredoxin and thioredoxin , the parasite has only one unique multifunctional enzyme, thioredoxin glutathione reductase (TGR) involving a fusion of two proteins, glutaredoxin (Grx) and thioredoxin reductase (TR), for performing all the redox activities. This dependence of S. mansoni on a single protein, TGR, for its protection from oxidative stress, makes it a promising drug target. Here, we describe a suitably validated, homology model for S. mansoni TGR (SmTGR), developed using both TR and Grx templates, functionally complete in the dimeric form with cofactors NADP(H) and FAD. Comparative analysis of substrate and inhibitor binding pockets of our model with crystal structures of parent TR as well as with that of glutathione reductase (GR), which is an essential component of the Grx system, appears to provide greater insight in to the functioning of TGR. This also augments recent observations reported on the basis of X-ray structure data on SmTGR monomer lacking the C-terminal selenocysteine tail. Keywords: Schistosoma mansoni; Thioredoxin glutathione reductase; Glutathione disulfide; Homology modeling; Docking