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101.
Anita Tragler Lakshmi Srinivasan Olga Shenderova Melvin McClauren Donald W. Brenner 《Molecular simulation》2013,39(1-2):121-130
Abstract A novel simulation interface is being developed as an educational tool to help students better understand fundamentals of materials science. This interface makes use of virtual reality (VR) technology consisting of PC-based graphics and a force-feedback haptic device. Visualization of atomistic processes with simultaneous tactile sensation via the haptic provides a powerful method for understanding complex phenomena that are otherwise difficult to comprehend. Modules are described that allow students to interactively explore interatomic bonding and single-atom diffusion through materials. 相似文献
102.
Bala Divya Mallavarapu Maaged Abdullah Shalini Saxena 《Journal of biomolecular structure & dynamics》2013,31(14):3751-3763
AbstractTuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (M.tb) or tubercule bacillus, and H37Rv is the most studied clinical strain. The recent development of resistance to existing drugs is a global health-care challenge to control and cure TB. Hence, there is a critical need to discover new drug targets in M.tb. The members of peptidoglycan biosynthesis pathway are attractive target proteins for antibacterial drug development. We have performed in silico analysis of M.tb MraY (Rv2156c) integral membrane protein and constructed the three-dimensional (3D) structure model of M.tb MraY based on homology modeling method. The validated model was complexed with antibiotic muraymycin D2 (MD2) and was used to generate structure-based pharmacophore model (e-pharmacophore). High-throughput virtual screening (HTVS) of Asinex database and molecular docking of hits was performed to identify the potential inhibitors based on their mode of interactions with the key residues involved in M.tb MraY–MD2 binding. The validation of these molecules was performed using molecular dynamics (MD) simulations for two best identified hit molecules complexed with M.tb MraY in the lipid bilayer, dipalmitoylphosphatidyl-choline (DPPC) membrane. The results indicated the stability of the complexes formed and retained non-bonding interactions similar to MD2. These findings may help in the design of new inhibitors to M.tb MraY involved in peptidoglycan biosynthesis. 相似文献
103.
A. R. Srinivasan Ramon Torres William Clark Wilma K. Olson 《Journal of biomolecular structure & dynamics》2013,31(3):459-496
Abstract A series of potential energy calculations have been carried out to estimate base sequence dependent structural differences in B-DNA. Attention has been focused on the simplest dimeric fragments that can be used to build long chains, computing the energy as a function of the orientation and displacement of the 16 possible base pair combinations within the double helix. Calculations have been performed, for simplicity, on free base pairs rather than complete nucleotide units. Conformational preferences and relative flexibilities are reported for various combinations of the roll, tilt, twist, lateral displacement, and propeller twist of individual residues. The predictions are compared with relevant experimental measures of conformation and flexibility, where available. The energy surfaces are found to fit into two distinct categories, some dimer duplexes preferring to bend in a symmetric fashion and others in a skewed manner. The effects of common chemical substitutions (uracil for thymine, 5-methyl cytosine for cytosine, and hypoxanthine for guanine) on the preferred arrangements of neighboring residues are also examined, and the interactions of the sugar-phosphate backbone are included in selected cases. As a first approximation, long range interactions between more distant neighbors, which may affect the local chain configuration, are ignored. A rotational isomeric state scheme is developed to describe the average configurations of individual dimers and is used to develop a static picture of overall double helical structure. The ability of the energetic scheme to account for documented examples of intrinsic B-DNA curvature is presented, and some new predictions of sequence directed chain bending are offered. 相似文献
104.
105.
The Fn14 and TWEAK are the receptor and ligand respectively and their mutual recognition and binding was reported to induce
pathogenesis of cancer and chronic autoimmune diseases. We had identified Fn14 as a novel target of low linear energy transfer
(LET) ionizing radiation in mice population. In the present study we generated the novel homology model of human Fn14,
optimized its energy and validated for authenticity by checking Ramachandran plot and also by calculating the RMSD. Based on
our earlier findings with Hippophae rhamnoides, a group of flavonoids and tannins were screened for their docking potential with
Fn14 at the site where its natural ligand TWEAK was binding. The comparative docking analysis showed that the order of docking,
from best to least, was Genistein, Rutin, Gallic acid ethyl ester and Quercetin, respectively. The findings predicted the radiomodifying
action of flavonoids and tannins. The study has immediate applications in development of non-toxic drugs/
nutraceuticals that may protect human population from harmful effects of radiation in various situations, such as nuclear accidents,
occupational exposure, diagnosis or radiotherapy. 相似文献
106.
Seetha V. Srinivasan David Dominguez-Sola Lily C. Wang Olivier Hyrien Jean Gautier 《Cell reports》2013,3(5):1629-1639
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107.
Sushma Prabhakara Supriya Khedkar Srikanth Mairpady Shambat Rajalakshmi Srinivasan Atanu Basu Anna Norrby-Teglund Aswin Sai Narain Seshasayee Gayathri Arakere 《PloS one》2013,8(3)
Staphylococcus aureus is a major human pathogen, first recognized as a leading cause of hospital-acquired infections. Community-associated S. aureus (CA-SA) pose a greater threat due to increase in severity of infection and disease among children and healthy adults. CA-SA strains in India are genetically diverse, among which is the sequence type (ST) 772, which has now spread to Australia, Europe and Japan. Towards understanding the genetic characteristics of ST772, we obtained draft genome sequences of five relevant clinical isolates and studied the properties of their PVL-carrying prophages, whose presence is a defining hallmark of CA-SA. We show that this is a novel prophage, which carries the structural genes of the hlb-carrying prophage and includes the sea enterotoxin. This architecture probably emerged early within the ST772 lineage, at least in India. The sea gene, unique to ST772 PVL, despite having promoter sequence characteristics typical of low expression, appears to be highly expressed during early phase of growth in laboratory conditions. We speculate that this might be a consequence of its novel sequence context. The crippled nature of the hlb-converting prophage in ST772 suggests that widespread mobility of the sea enterotoxin might be a selective force behind its ‘transfer’ to the PVL prophage. Wild type ST772 strains induced strong proliferative responses as well as high cytotoxic activity against neutrophils, likely mediated by superantigen SEA and the PVL toxin respectively. Both proliferation and cytotoxicity were markedly reduced in a cured ST772 strain indicating the impact of the phage on virulence. The presence of SEA alongside the genes for the immune system-modulating PVL toxin may contribute to the success and virulence of ST772. 相似文献
108.
Mithun Das Jin Sha Bertha Hidalgo Stella Aslibekyan Anh N. Do Degui Zhi Dianjianyi Sun Tao Zhang Shengxu Li Wei Chen Sathanur R. Srinivasan Hemant K. Tiwari Devin Absher Jose M. Ordovas Gerald S. Berenson Donna K. Arnett Marguerite R. Irvin 《PloS one》2016,11(1)
In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10−7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10-14 and P for cg17058475 = 1.2x10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future. 相似文献
109.
Background
Detection of Polyomavirus (PyV) DNA in metropolitan rivers worldwide has led to the suggestion that primary viral infection can occur by the oral route. The aim of this study was to test this notion experimentally.Methods
Mouse PyV (MPyV) was used to infect C57BL/6J mice by the nasal or intragastric route. Viral load kinetics was studied 3, 7, 10, 14, 21 and 28 days post-infection (dpi) using quantitative PCR.Results
Following nasal infection, MPyV DNA was readily detected in many organs including lung, heart, aorta, colon, and stool with viral loads in the range of 103–106 copies/mg wet weight that peaked 7–10 dpi. Complete viral clearance occurred in the serum and kidney by 28 dpi, while clearance in other organs was partial with a 10–100 fold decrease in viral load. In contrast, following intragastric infection peak detection of PyV was delayed to 21 dpi, and viral loads were up to 3 logs lower. There was no detectable virus in the heart, colon, or stool.Conclusions
The intragastric route of MPyV infection is successful, not as efficacious as the respiratory route, and associated with delayed viral dissemination as well as a lower peak MPyV load in individual organs. 相似文献110.
Enrico Munari Alcides Chaux Ajay M. Vaghasia Diana Taheri Sarah Karram Stephania M. Bezerra Nilda Gonzalez Roibon William G. Nelson Srinivasan Yegnasubramanian George J. Netto Michael C. Haffner 《PloS one》2016,11(1)
Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment. 相似文献