scholarly journals Mining of Microbial Genomes for the Novel Sources of Nitrilases

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Nikhil Sharma ◽  
Neerja Thakur ◽  
Tilak Raj ◽  
Savitri ◽  
Tek Chand Bhalla
Keyword(s):  
In Silico ◽  
Sequence Data ◽  
Potassium Cyanide ◽  
Amino Acid Sequences ◽  
The Novel ◽  
Microbial Genomes ◽  
Aryl Nitriles ◽  
Aliphatic Nitriles ◽  
Cyanide Dihydratase

Next-generation DNA sequencing (NGS) has made it feasible to sequence large number of microbial genomes and advancements in computational biology have opened enormous opportunities to mine genome sequence data for novel genes and enzymes or their sources. In the present communication in silico mining of microbial genomes has been carried out to find novel sources of nitrilases. The sequences selected were analyzed for homology and considered for designing motifs. The manually designed motifs based on amino acid sequences of nitrilases were used to screen 2000 microbial genomes (translated to proteomes). This resulted in identification of one hundred thirty-eight putative/hypothetical sequences which could potentially code for nitrilase activity. In vitro validation of nine predicted sources of nitrilases was done for nitrile/cyanide hydrolyzing activity. Out of nine predicted nitrilases, Gluconacetobacter diazotrophicus, Sphingopyxis alaskensis, Saccharomonospora viridis, and Shimwellia blattae were specific for aliphatic nitriles, whereas nitrilases from Geodermatophilus obscurus, Nocardiopsis dassonvillei, Runella slithyformis, and Streptomyces albus possessed activity for aromatic nitriles. Flavobacterium indicum was specific towards potassium cyanide (KCN) which revealed the presence of nitrilase homolog, that is, cyanide dihydratase with no activity for either aliphatic, aromatic, or aryl nitriles. The present study reports the novel sources of nitrilases and cyanide dihydratase which were not reported hitherto by in silico or in vitro studies.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

scholarly journals The Bioactivity Prediction of Peptides from Tuna Skin Collagen Using Integrated Method Combining In Vitro and In Silico

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2739
Author(s):  
Liza Devita ◽  
Hanifah Nuryani Lioe ◽  
Mala Nurilmala ◽  
Maggy T. Suhartono
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Weight Fraction ◽  
Amino Acid Sequences ◽  
Skin Collagen ◽  
Dpph Method ◽  
Peptide Fractions

The hydrolysates and peptide fractions of bigeye tuna (Thunnus obesus) skin collagen have been successfully studied. The hydrolysates (HPA, HPN, HPS, HBA, HBN, HBS) were the result of the hydrolysis of collagen using alcalase, neutrase, and savinase. The peptide fractions (PPA, PPN, PPS, PBA, PBN, PBS) were the fractions obtained following ultrafiltration of the hydrolysates. The antioxidant activities of the hydrolysates and peptide fractions were studied using the DPPH method. The effects of collagen types, enzymes, and molecular sizes on the antioxidant activities were analyzed using profile plots analysis. The amino acid sequences of the peptides in the fraction with the highest antioxidant activity were analyzed using LC-MS/MS. Finally, their bioactivity and characteristics were studied using in silico analysis. The hydrolysates and peptide fractions provided antioxidant activity (6.17–135.40 µmol AAE/g protein). The lower molecular weight fraction had higher antioxidant activity. Collagen from pepsin treatment produced higher activity than that of bromelain treatment. The fraction from collagen hydrolysates by savinase treatment had the highest activity compared to neutrase and alcalase treatments. The peptides in the PBN and PPS fractions of <3 kDa had antidiabetic, antihypertensive and antioxidant activities. In conclusion, they have the potential to be used in food and health applications.

scholarly journals Astaxanthin-Mediated Bacterial Lethality: Evidence from Oxidative Stress Contribution and Molecular Dynamics Simulation

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Jamiu Olaseni Aribisala ◽  
Sonto Nkosi ◽  
Kehinde Idowu ◽  
Ismaila Olanrewaju Nurain ◽  
Gaositwe Melvin Makolomakwa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Current Knowledge ◽  
Dynamics Simulation ◽  
The Novel ◽  
Topoisomerase Iv ◽  
Test Organisms ◽  
Gyrase A ◽  
Vitro Analysis

The involvement of cellular oxidative stress in antibacterial therapy has remained a topical issue over the years. In this study, the contribution of oxidative stress to astaxanthin-mediated bacterial lethality was evaluated in silico and in vitro. For the in vitro analysis, the minimum inhibitory concentration (MIC) of astaxanthin was lower than that of novobiocin against Staphylococcus aureus but generally higher than those of the reference antibiotics against other test organisms. The level of superoxide anion of the tested organisms increased significantly following treatment with astaxanthin when compared with DMSO-treated cells. This increase compared favorably with those observed with the reference antibiotics and was consistent with a decrease in the concentration of glutathione (GSH) and corresponding significant increase in ADP/ATP ratio. These observations are suggestive of probable involvement of oxidative stress in antibacterial capability of astaxanthin and in agreement with the results of the in silico evaluations, where the free energy scores of astaxanthins’ complexes with topoisomerase IV ParC and ParE were higher than those of the reference antibiotics. These observations were consistent with the structural stability and compactness of the complexes as astaxanthin was observed to be more stable against topoisomerase IV ParC and ParE than DNA Gyrase A and B. Put together, findings from this study underscored the nature and mechanism of antibacterial action of astaxanthin that could suggest practical approaches in enhancing our current knowledge of antibacterial arsenal and aid in the novel development of alternative natural topo2A inhibitor.

scholarly journals The Capsid Binder Vapendavir and the Novel Protease Inhibitor SG85 Inhibit Enterovirus 71 Replication

2014 ◽  
Vol 58 (11) ◽  
pp. 6990-6992 ◽  
Author(s):  
Aloys Tijsma ◽  
David Franco ◽  
Simon Tucker ◽  
Rolf Hilgenfeld ◽  
Mathy Froeyen ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
In Silico ◽  
Enterovirus 71 ◽  
Docking Study ◽  
Viral Capsid ◽  
The Novel ◽  
Binding Interactions

ABSTRACTAntivirals against enterovirus 71 (EV71) are urgently needed. We demonstrate that the novel enteroviral protease inhibitor (PI) SG85 and capsid binder (CB) vapendavir efficiently inhibit thein vitroreplication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C. The PI rupintrivir, the CB pirodavir, and the host-targeting compound enviroxime, which were included as reference compounds, also inhibited the replication of all isolates. Remarkably, the CB compound pleconaril was devoid of any anti-EV71 activity. Anin silicodocking study revealed that pleconaril—unlike vapendavir and pirodavir—lacks essential binding interactions with the viral capsid. Vapendavir and SG85 (or analogues) should be further explored for the treatment of EV71 infections. The data presented here may serve as a reference when developing yet-novel inhibitors.

Molecular mechanism of tobramycin with human serum albumin for probing binding interactions: multi-spectroscopic and computational approaches

2017 ◽  
Vol 41 (16) ◽  
pp. 8203-8213 ◽  
Author(s):  
Muslim Raza ◽  
Yun Wei ◽  
Yang Jiang ◽  
Aftab Ahmad ◽  
Saleem Raza ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Site ◽  
Molecular Mechanism ◽  
In Silico ◽  
The Novel ◽  
Binding Interactions ◽  
Computational Approaches

Highlighting novelty: comprehensive in vitro and in silico insights for understanding the novel binding site of TOB with HSA.

scholarly journals Characterization of rare ABCC8 variants identified in Spanish pulmonary arterial hypertension patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mauro Lago-Docampo ◽  
Jair Tenorio ◽  
Ignacio Hernández-González ◽  
Carmen Pérez-Olivares ◽  
Pilar Escribano-Subías ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
In Silico ◽  
Rare Variants ◽  
The Novel ◽  
Structural Protein ◽  
Uncertain Significance ◽  
Pulmonary Arterial ◽  
Biochemical Analyses

Abstract Pulmonary Arterial Hypertension (PAH) is a rare and fatal disease where knowledge about its genetic basis continues to increase. In this study, we used targeted panel sequencing in a cohort of 624 adult and pediatric patients from the Spanish PAH registry. We identified 11 rare variants in the ATP-binding Cassette subfamily C member 8 (ABCC8) gene, most of them with splicing alteration predictions. One patient also carried another variant in SMAD1 gene (c.27delinsGTAAAG). We performed an ABCC8 in vitro biochemical analyses using hybrid minigenes to confirm the correct mRNA processing of 3 missense variants (c.211C > T p.His71Tyr, c.298G > A p.Glu100Lys and c.1429G > A p.Val477Met) and the skipping of exon 27 in the novel splicing variant c.3394G > A. Finally, we used structural protein information to further assess the pathogenicity of the variants. The results showed 11 novel changes in ABCC8 and 1 in SMAD1 present in PAH patients. After in silico and in vitro biochemical analyses, we classified 2 as pathogenic (c.3288_3289del and c.3394G > A), 6 as likely pathogenic (c.211C > T, c.1429G > A, c.1643C > T, c.2422C > A, c.2694 + 1G > A, c.3976G > A and SMAD1 c.27delinsGTAAAG) and 3 as Variants of Uncertain Significance (c.298G > A, c.2176G > A and c.3238G > A). In all, we show that coupling in silico tools with in vitro biochemical studies can improve the classification of genetic variants.

A comprehensive pharmacokinetic/pharmacodynamics analysis of the novel IGF1R/INSR inhibitor BI 893923 applying in vitro, in vivo and in silico modeling techniques

2016 ◽  
Vol 77 (6) ◽  
pp. 1303-1314 ◽  
Author(s):  
Melanie I. Titze ◽  
Otmar Schaaf ◽  
Marco H. Hofmann ◽  
Michael P. Sanderson ◽  
Stephan K. Zahn ◽  
...  
Keyword(s):  
In Silico ◽  
The Novel ◽  
In Silico Modeling ◽  
Modeling Techniques

scholarly journals Fungal Genomic Resources for Strain Identification and Diversity Analysis of 1900 Fungal Species

2021 ◽  
Vol 7 (4) ◽  
pp. 288
Author(s):  
Mir Asif Iquebal ◽  
Sarika Jaiswal ◽  
Vineet Kumar Mishra ◽  
Rahul Singh Jasrotia ◽  
Ulavappa B. Angadi ◽  
...  
Keyword(s):  
Genome Sequence ◽  
In Silico ◽  
Sequence Data ◽  
Fungal Species ◽  
Genomic Research ◽  
Whole Genome Sequence ◽  
Strain Identification ◽  
Diversity Analysis ◽  
Whole Genome

Identification and diversity analysis of fungi is greatly challenging. Though internal transcribed spacer (ITS), region-based DNA fingerprinting works as a “gold standard” for most of the fungal species group, it cannot differentiate between all the groups and cryptic species. Therefore, it is of paramount importance to find an alternative approach for strain differentiation. Availability of whole genome sequence data of nearly 2000 fungal species are a promising solution to such requirement. We present whole genome sequence-based world’s largest microsatellite database, FungSatDB having >19M loci obtained from >1900 fungal species/strains using >4000 assemblies across globe. Genotyping efficacy of FungSatDB has been evaluated by both in-silico and in-vitro PCR. By in silico PCR, 66 strains of 8 countries representing four continents were successfully differentiated. Genotyping efficacy was also evaluated by in vitro PCR in four fungal species. This approach overcomes limitation of ITS in species, strain signature, and diversity analysis. It can accelerate fungal genomic research endeavors in agriculture, industrial, and environmental management.

scholarly journals A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
David Wylensek ◽  
Thomas C. A. Hitch ◽  
Thomas Riedel ◽  
Afrizal Afrizal ◽  
Neeraj Kumar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Bile Acids ◽  
Sequence Data ◽  
Novel Species ◽  
Meta Analysis ◽  
Gene Clusters ◽  
In Vitro Assays ◽  
The Novel ◽  
Strain Collection

AbstractOur knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called ‘Pig intestinal bacterial collection’ (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota.

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