IN-SILICO ANALYSIS OF SELECTED FLAVONOIDS WITH TUMOUR NECROSIS FACTOR USING MODERN COMPUTATIONAL TOOLS

Bifidobacteria are among the most abundant microorganisms inhabiting the intestine of humans and many animals. Within the genus Bifidobacterium, several beneficial effects have been attributed to strains belonging to the subspecies Bifidobacterium longum subsp. longum and Bifidobacterium longum subsp. infantis, which are often found in infants and adults. The increasing numbers of sequenced genomes belonging to these two subspecies, and the availability of novel computational tools focused on predicting glycolytic abilities, with the aim of understanding the capabilities of degrading specific carbohydrates, allowed us to depict the potential glycoside hydrolases (GH) of these bacteria, with a focus on those GH profiles that differ in the two subspecies. We performed an in silico examination of 188 sequenced B. longum genomes and depicted the commonly present and strain-specific GHs and GH families among representatives of this species. Additionally, GH profiling, genome-based and 16S rRNA-based clustering analyses showed that the subspecies assignment of some strains does not properly match with their genetic background. Furthermore, the analysis of the potential GH component allowed the distinction of clear GH patterns. Some of the GH activities, and their link with the two subspecies under study, are further discussed. Overall, our in silico analysis poses some questions about the suitability of considering the GH activities of B. longum subsp. longum and B. longum subsp. infantis to gain insight into the characterization and classification of these two subspecies with probiotic interest.

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Evaluation of Computationally Designed Peptides against TWEAK, a Cytokine of the Tumour Necrosis Factor Ligand Family

International Journal of Molecular Sciences ◽

10.3390/ijms22031066 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1066

Author(s):

Miriam Badia-Villanueva ◽

Sira Defaus ◽

Ruben Foj ◽

David Andreu ◽

Baldo Oliva ◽

...

Keyword(s):

Tumour Necrosis Factor ◽

Protein Interactions ◽

In Silico ◽

Tumour Necrosis ◽

In Vitro Assays ◽

Physical Interaction ◽

Vitro Assay ◽

Starting Point ◽

Necrosis Factor

The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumour necrosis factor ligand family and has been shown to be overexpressed in tumoral cells together with the fibroblast growth factor–inducible 14 (Fn14) receptor. TWEAK-Fn14 interaction triggers a set of intracellular pathways responsible for tumour cell invasion and migration, as well as proliferation and angiogenesis. Hence, modulation of the TWEAK-Fn14 interaction is an important therapeutic goal. The targeting of protein-protein interactions by external agents, e.g., drugs, remains a substantial challenge. Given their intrinsic features, as well as recent advances that improve their pharmacological profiles, peptides have arisen as promising agents in this regard. Here, we report, by in silico structural design validated by cell-based and in vitro assays, the discovery of four peptides able to target TWEAK. Our results show that, when added to TWEAK-dependent cellular cultures, peptides cause a down-regulation of genes that are part of TWEAK-Fn14 signalling pathway. The direct, physical interaction between the peptides and TWEAK was further elucidated in an in vitro assay which confirmed that the bioactivity shown in cell-based assays was due to the targeting of TWEAK. The results presented here are framed within early pre-clinical drug development and therefore these peptide hits represent a starting point for the development of novel therapeutic agents. Our approach exemplifies the powerful combination of in silico and experimental efforts to quickly identify peptides with desirable traits.

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In Silico Analysis of Tumor Necrosis Factor α-Induced Protein 8-Like-1 (TIPE1) Protein

PLoS ONE ◽

10.1371/journal.pone.0134114 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0134114 ◽

Cited By ~ 3

Author(s):

Pei Shen ◽

Hong Zhang ◽

Zhaoliang Su ◽

Shengjun Wang ◽

Huaxi Xu

Keyword(s):

Tumor Necrosis Factor ◽

In Silico ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

In Silico Analysis ◽

Factor Α ◽

Silico Analysis ◽

Necrosis Factor

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In Silico Study of the Resistance to Organophosphorus Pesticides Associated with Point Mutations in Acetylcholinesterase of Lepidoptera: B. mandarina, B. mori, C. auricilius, C. suppressalis, C. pomonella, H. armígera, P. xylostella, S. frugiperda, and S. litura

International Journal of Molecular Sciences ◽

10.3390/ijms20102404 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2404

Author(s):

Francisco Reyes-Espinosa ◽

Domingo Méndez-Álvarez ◽

Miguel A. Pérez-Rodríguez ◽

Verónica Herrera-Mayorga ◽

Alfredo Juárez-Saldivar ◽

...

Keyword(s):

Molecular Docking ◽

In Silico ◽

Structural Modification ◽

Organophosphorus Pesticides ◽

Point Mutations ◽

In Silico Analysis ◽

Computational Tools ◽

Structural Modifications ◽

In Silico Study ◽

Silico Analysis

An in silico analysis of the interaction between the complex-ligands of nine acetylcholinesterase (AChE) structures of Lepidopteran organisms and 43 organophosphorus (OPs) pesticides with previous resistance reports was carried out. To predict the potential resistance by structural modifications in Lepidoptera insects, due to proposed point mutations in AChE, a broad analysis was performed using computational tools, such as homology modeling and molecular docking. Two relevant findings were revealed: (1) Docking results give a configuration of the most probable spatial orientation of two interacting molecules (AChE enzyme and OP pesticide) and (2) a predicted ΔGb. The mutations evaluated in the form 1 acetylcholinesterase (AChE-1) and form 2 acetylcholinesterase (AChE-2) structures of enzymes do not affect in any way (there is no regularity of change or significant deviations) the values of the binding energy (ΔGb) recorded in the AChE–OPs complexes. However, the mutations analyzed in AChE are associated with a structural modification that causes an inadequate interaction to complete the phosphorylation of the enzyme.

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A comprehensive in silico analysis, distribution and frequency of human Nkx2-5 mutations; A critical gene in congenital heart disease

Journal of Cardiovascular and Thoracic Research ◽

10.15171/jcvtr.2019.47 ◽

2019 ◽

Vol 11 (4) ◽

pp. 287-299 ◽

Cited By ~ 1

Author(s):

Samira Kalayinia ◽

Serwa Ghasemi ◽

Nejat Mahdieh

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

High Frequency ◽

In Silico ◽

Congenital Heart ◽

In Silico Analysis ◽

Computational Tools ◽

Phred Score ◽

Functional Consequences ◽

Silico Analysis

Introduction: Congenital heart disease (CHD) affects 1% to 2 % of live births. The Nkx2-5 gene, is known as the significant heart marker during embryonic evolution and it is also necessary for the survival of cardiomyocytes and homeostasis in adulthood. In this study, Nkx2-5 mutations are investigated to identify the frequency, distribution, functional consequences of mutations by using computational tools. <br /> Methods: A complete literature search was conducted to find Nkx2-5 mutations using the following key words: Nkx2-5 and/or CHD and mutations. The mutations were in silico analyzed using tools which predict the pathogenicity of the variants. A picture of Nkx2-5 protein and functional or structural effects of its variants were also figured using I-TASSER and STRING.<br /> Results: A total number of 105 mutations from 18 countries were introduced. The most (24.1%) and the least (1.49%) frequency of Nkx2-5 mutations were observed in Europe and Africa, respectively. The c.73C>T and c.533C>T mutations are distributed worldwide. c.325G>T (62.5%) and c.896A>G (52.9%) had the most frequency. The most numbers of Nkx2-5 mutations were reported from Germany. The c.541C>T had the highest CADD score (Phred score = 38) and the least was for c.380C>A (Phred score=0.002). 41.9% of mutations were predicted as potentially pathogenic by all prediction tools. <br /> Conclusion: This is the first report of the Nkx2-5 mutations evaluation in the worldwide. Given that the high frequency of mutation in Germany, and also some mutations were seen only in this country, therefore, presumably the main origin of Nkx2-5 mutations arise from Germany.

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Discovery in Silico and Characterization in Vitro of Novel Genes Exclusively Expressed in the Mouse Epididymis

Molecular Endocrinology ◽

10.1210/me.2003-0008 ◽

2003 ◽

Vol 17 (11) ◽

pp. 2138-2151 ◽

Cited By ~ 47

Author(s):

Jenni Penttinen ◽

Dwi Ari Pujianto ◽

Petra Sipilä ◽

Ilpo Huhtaniemi ◽

Matti Poutanen

Keyword(s):

Expressed Sequence Tags ◽

In Silico ◽

In Silico Analysis ◽

Rnase A ◽

Computational Tools ◽

Cdna Sequences ◽

Expressed Sequence ◽

Silico Analysis ◽

Mouse Epididymis

Abstract Epididymal proteins interact with sperm during their passage through the epididymis and thus contribute to the maturation and fertilizing capacity of the spermatozoa. In the present study we have discovered five novel epididymis-specific genes through in silico analysis of expressed sequence tags (ESTs) at the UniGene library collection. The strategy used is a powerful way to discover novel epididymis-specific genes. The full-length cDNA sequences were determined, and computational tools were used to characterize the genomic structures and to predict putative functions for the encoded proteins. In vitro analyses revealed that all five genes characterized were highly expressed in the defined areas of the epididymis, and they were not expressed at significant levels in any other tissue. Three of the genes were named on the basis of their putative functions: Spint4 (serine protease inhibitor, Kunitz type 4), and Rnase9 and Rnase10 (ribonuclease, Rnase A family 9 and 10), while for the ESTs AV381130 and AV381126 no putative functions could be predicted. The expression of Spint4, Rnase9, and AV381130 was found to be under a direct or indirect regulation by androgens, while the expression of Rnase10 is regulated by a testicular factor(s) other than androgen. None of the genes were expressed in the immature epididymis, while mRNAs were detected from d 17 onward, at the time of maturation of epididymal epithelium. However, the expression of AV381130 was not detected until d 30 after birth, indicating a close connection between gene expression and puberty.

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Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

Biochemical Society Symposium ◽

10.1042/bss0700039 ◽

2003 ◽

Vol 70 ◽

pp. 39-52 ◽

Cited By ~ 54

Author(s):

Roy A. Black ◽

John R. Doedens ◽

Rajeev Mahimkar ◽

Richard Johnson ◽

Lin Guo ◽

...

Keyword(s):

Substrate Specificity ◽

Recent Work ◽

Tumour Necrosis Factor ◽

Tumour Necrosis ◽

Transforming Growth Factor ◽

Intrinsic Activity ◽

Converting Enzyme ◽

Tumour Necrosis Factor Α ◽

Factor Α ◽

Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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