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91.
Richa Mudgal Ramanathan Sowdhamini Nagasuma Chandra Narayanaswamy Srinivasan Sankaran Sandhya 《Journal of molecular biology》2014
Protein functional annotation relies on the identification of accurate relationships, sequence divergence being a key factor. This is especially evident when distant protein relationships are demonstrated only with three-dimensional structures. To address this challenge, we describe a computational approach to purposefully bridge gaps between related protein families through directed design of protein-like “linker” sequences. For this, we represented SCOP domain families, integrated with sequence homologues, as multiple profiles and performed HMM-HMM alignments between related domain families. Where convincing alignments were achieved, we applied a roulette wheel-based method to design 3,611,010 protein-like sequences corresponding to 374 SCOP folds. To analyze their ability to link proteins in homology searches, we used 3024 queries to search two databases, one containing only natural sequences and another one additionally containing designed sequences. Our results showed that augmented database searches showed up to 30% improvement in fold coverage for over 74% of the folds, with 52 folds achieving all theoretically possible connections. Although sequences could not be designed between some families, the availability of designed sequences between other families within the fold established the sequence continuum to demonstrate 373 difficult relationships. Ultimately, as a practical and realistic extension, we demonstrate that such protein-like sequences can be “plugged-into” routine and generic sequence database searches to empower not only remote homology detection but also fold recognition. Our richly statistically supported findings show that complementary searches in both databases will increase the effectiveness of sequence-based searches in recognizing all homologues sharing a common fold. 相似文献
92.
D Ranganathan S Kurur A C Kunwar A V Sarma M Vairamani I L Karle 《The journal of peptide research》2000,56(6):416-426
The design, synthesis, characterization and self-assembling properties of a new class of amphiphilic peptides, constructed from a bifunctional polar core attached to totally hydrophobic arms, are presented. The first series of this class, represented by the general structure Py(Aibn)2 (Py=2,6-pyridine dicarbonyl unit; Aib=alpha, alpha'-dimethyl glycine; n=1-4), is prepared in a single step by the condensation of commercially available 2,6-pyridine dicarbonyl dichloride with the methyl ester of homo oligoAib peptide (Aibn-OMe) in the presence of triethyl amine. 1H NMR VT and ROESY studies indicated the presence of a common structural feature of 2-fold symmetry and an NH...N hydrogen bond for all the members. Whereas the Aib3 segment in Py(Aib3)2 showed only the onset of a 3(10)-helical structure, the presence of a well-formed 3(10)-helix in both Aib4 arms of Py(Aib4)2 was evident in the 1H NMR of the bispeptide. X-ray crystallographic studies have shown that in the solid state, whereas Py(Aib2)2 molecules organize into a sheet-like structure and Py(Aib3)2 molecules form a double-stranded string assembly, the tetra Aib bispeptide, Py(Aib4)2, is organized to form a tetrameric assembly which in turn extends into a continuous channel-like structure. The channel is totally hydrophobic in the interior and can selectively encapsulate lipophilic ester (CH3COOR, R=C2H5, C5H11) molecules, as shown by the crystal structures of the encapsulating channel. The crystal structure parameters are: 1b, Py(Aib2)2, C25H37N5O8, sp. gr. P2(1)2(1)2(1), a=9.170(1) A, b=16.215(2) A, c=20.091(3) A, R=4.80; 1c, Py(Aib3)2, C33H51N7O10H2O, sp. gr. P1, a=11.040(1) A, b=12.367(1) A, c=16.959(1) A, alpha =102.41 degrees, beta =97.29 degrees, gamma =110.83 degrees, R1=6.94; 1 da, Py(Aib4)2.et ac, C41H65N9O12.1.5H2O.C4H8O2, sp. gr. P1, a=16.064(4) A, b=16.156 A, c=21.655(5) A, alpha =90.14(1)degrees, beta=101.38(2) degrees, gamma=97.07(1)degrees, Z=4, R1=9.03; 1db, Py(Aib4)2.amylac, C41H65N9O12.H2O.C7H14O2, P2(1)/c, a=16.890(1) A, b=17.523(1)A, c=20.411(1) A, beta=98.18 degrees, Z=4, R=11.1 (with disorder). 相似文献
93.
E Y Wu C C Hsia A S Estrera R H Epstein M Ramanathan R L Johnson 《Journal of applied physiology》2000,89(1):182-191
To determine the role of mediastinal shift after pneumonectomy (PNX) on compensatory responses, we performed right PNX in adult dogs and replaced the resected lung with a custom-shaped inflatable silicone prosthesis. Prosthesis was inflated (Inf) to prevent mediastinal shift, or deflated (Def), allowing mediastinal shift to occur. Thoracic, lung air, and tissue volumes were measured by computerized tomography scan. Lung diffusing capacities for carbon monoxide (DL(CO)) and its components, membrane diffusing capacity for carbon monoxide (Dm(CO)) and capillary blood volume (Vc), were measured at rest and during exercise by a rebreathing technique. In the Inf group, lung air volume was significantly smaller than in Def group; however, the lung became elongated and expanded by 20% via caudal displacement of the left hemidiaphragm. Consequently, rib cage volume was similar, but total thoracic volume was higher in the Inf group. Extravascular septal tissue volume was not different between groups. At a given pulmonary blood flow, DL(CO) and Dm(CO) were significantly lower in the Inf group, but Vc was similar. In one dog, delayed mediastinal shift occurred 9 mo after PNX; both lung volume and DL(CO) progressively increased over the subsequent 3 mo. We conclude that preventing mediastinal shift after PNX impairs recruitment of diffusing capacity but does not abolish expansion of the remaining lung or the compensatory increase in extravascular septal tissue volume. 相似文献
94.
Although adoption of newer Point-of-Care (POC) diagnostics is increasing, there is a significant challenge using POC diagnostics data to improve epidemiological models. In this work, we propose a method to process zip-code level POC datasets and apply these processed data to calibrate an epidemiological model. We specifically develop a calibration algorithm using simulated annealing and calibrate a parsimonious equation-based model of modified Susceptible-Infected-Recovered (SIR) dynamics. The results show that parsimonious models are remarkably effective in predicting the dynamics observed in the number of infected patients and our calibration algorithm is sufficiently capable of predicting peak loads observed in POC diagnostics data while staying within reasonable and empirical parameter ranges reported in the literature. Additionally, we explore the future use of the calibrated values by testing the correlation between peak load and population density from Census data. Our results show that linearity assumptions for the relationships among various factors can be misleading, therefore further data sources and analysis are needed to identify relationships between additional parameters and existing calibrated ones. Calibration approaches such as ours can determine the values of newly added parameters along with existing ones and enable policy-makers to make better multi-scale decisions. 相似文献
95.
96.
Divalent metal ions (Fe2+, Cu2+, Zn2+, Ni2+, and Mn2+) induced lipid oxidation in cooked, but not in raw fish. The extent of lipid oxidation, measured by the production of thiobarbituric
acid reactive substances (TBRS), was increased with higher concentrations of iron, zinc, and nickel, but was decreased with
increasing concentrations of copper and manganese. The natural products: ellagic acid, tannic acid, myricetin, and quercetin,
inhibited lipid oxidation in cooked fish. The enhanced lipid oxidation caused by cupric ions (103 pmol/100 g fish) was also inhibited by the natural products. The degree of inhibition in copper-treated fish, however, was
less than that in fish that had no added copper. The inhibition was concentration dependent. The antioxidative potency of
the various natural products was independent of the type of metal ion-induced lipid oxidation. Ellagic acid was the most potent
antioxidant (75.7–83.9%), followed by tannic acid (60.4–77.3%), myricetin (52.9–70.4%), and quercetin (32.6–44.2%). 相似文献
97.
98.
99.
Murugesan Sivaranjani Ramanathan Srinivasan Chairmandurai Aravindraja Shunmugiah Karutha Pandian 《Biofouling》2018,34(5):579-593
The present study was designed to investigate the anti-biofilm potential of alpha-mangostin (α-MG) against Acinetobacter baumannii (AB). The biofilm inhibitory concentration (BIC) of α-MG against AB was found to be 2 μg ml?1. α-MG (0.5, 1 and 2 μg ml?1) exhibited non-bactericidal concentration-dependent anti-biofilm activities against AB. However, α-MG failed to disintegrate the mature biofilms of AB even at a 10-fold increased concentration from its BIC. Results from qRT-PCR and in vitro bioassays further demonstrated that α-MG downregulated the expression of bfmR, pgaA, pgaC, csuA/B, ompA, bap, katE, and sodB genes, which correspondingly affects biofilm formation and its associated virulence traits. The present study suggests that α-MG exerts its anti-biofilm property by interrupting initial biofilm formation and the cell-to-cell signaling mechanism of AB. Additional studies are required to understand the mode of action responsible for the anti-biofilm property. 相似文献
100.
Computational genomic analysis of hemorrhagic fever viruses 总被引:6,自引:0,他引:6
A number of distinct viruses are known as hemorrhagic fever viruses based on a shared ability to induce hemorrhage by poorly
understood mechanisms, typically involving the formation of blood clots (“disseminated intravascular coagulation”). It is
well documented that selenium plays a significant role in the regulation of blood clotting via its effects on the thromboxane/prostacyclin
ratio, and effects on the complement system. Selenium has an anticlotting effect, whereas selenium deficiency has a proclotting
or thrombotic effect. It is also well documented that extreme dietary selenium deficiency, which is almost never seen in humans,
has been associated with hemorrhagic effects in animals. Thus, the possibility that viral selenoprotein synthesis might contribute
to hemorrhagic symptoms merits further consideration. Computational genomic analysis of certain hemorrhagic fever viruses
reveals the presence of potential protein coding regions (PPCRs) containing large numbers of in-frame UGA codons, particularly
in the −1 reading frame. In some cases, these clusterings of UGA codons are very unlikely to have arisen by chance, suggesting
that these UGAs may have some function other than being a stop codon, such as encoding selenocysteine. For this to be possible,
a downstream selenocysteine insertion element (SECIS) is required. Ebola Zaire, the most notorious hemorrhagic fever virus,
has a PPCR with 17 UGA codons, and several potential SECIS elements can be identified in the viral genome. One potential viral
selenoprotein may contain up to 16 selenium atoms per molecule. Biosynthesis of this protein could impose an unprecedented
selenium demand on the host, potentially leading to severe lipid peroxidation and cell membrane destruction, and contributing
to hemorrhagic symptoms. Alternatively, even in the absence of programmed selenoprotein synthesis, it is possible that random
slippage errors would lead to increased encounters with UGA codons in overlapping reading frames, and thus potentially to
nonspecific depletion of SeC in the host. 相似文献