scholarly journals Immunoinformatics Approach for Designing Multiple Epitope-Based Vaccine against Human Metapneumovirus Utilizing its Fusion Protein.

2020 ◽  
Author(s):  
Ibtihal A Ahmed ◽  
Mosab Y Alnour ◽  
Nafisa M Eisa ◽  
Esameldeen A Adam ◽  
Faiza A Omer ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Respiratory Infections ◽  
3D Structure ◽  
Experimental Studies ◽  
Docking Study ◽  
Human Metapneumovirus ◽  
Web Servers ◽  
Molecular Docking Study ◽  
Mhc I ◽  
Mhc Ii

Abstract BackgroundHuman Metapneumovirus is a major cause of acute respiratory infections especially in children besides it’s responsible for substantial hospitalizations associated with significant morbidity and treatment cost. Hence vaccination is required. Consequently, we aim to predict effective, safe, and universal epitope-based peptides vaccine against the HMPV using its Fusion Protein via the Immunoinformatics approach since there are no licensed vaccines or antiviral treatments yet.To achieve this goal, various Immunoinformatics databases and web servers, including, the Immune Epitope Database used the Allergen FP v.1.0, and ToxinPred web servers as well as Phyre2 web portal for the modeling of peptide 3D structure and molecular docking study on Cresset Flare software.Result According to the results, the peptide GSTVYYPN was the best predicted B-cells epitopes. Moreover, the peptide VIYMVQLPI with population coverage 48.27% in class(C) I, 35.12% in (C)II, and the peptides LIGVYGSSV with 44.03% in C II, YTNVFTLEV with 61.92% in class I were the best-predicted T-cells epitopes that will interact effectively with the MHC I and MHC II molecules respectively.Conclusions We recommend the use of them, the highest coverage, and the best -combined allele’s bindings of immunogenic multiple peptide vaccines. Also, experimental studies recommend validating the results.

scholarly journals Molecular docking study on quercetin derivatives as inhibitors of PantothenateSynthetase (PanC) of Mycobacterium tuberculosis

2020 ◽  
Vol 11 (3) ◽  
pp. 3684-3690
Author(s):  
Premalatha E ◽  
Dineshraj R ◽  
Iyanar Kannan ◽  
Bhaarath KS ◽  
Sharavanan TKV
Keyword(s):  
3D Structure ◽  
Acid Synthesis ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Quercetin Derivatives ◽  
Pantothenate Synthetase ◽  
Docking Tool ◽  
Critical Components ◽  
Derivatives Of

The anti-TB drugs currently in the use are insufficient to address these major health challenges. Hence, it is imperative to discover and develop new and efficient drugs against TB. The enzyme pantothenate synthetase (PS or PanC), necessary for the production of pantothenate (vitamin B5), critical components of fatty acid synthesis, when inhibited will in turn affect the cell wall synthesis of bacilli. In the present study, an attempt will be made to find the drug like molecules from quercetin derivatives prepared in silico to find out possible inhibitors of PanCof M. tuberculosis. The 3D structure of PanC was obtained from RCSB database and quercetin from ZINC database. The derivatives of quercetin were prepared and were docked initially with iGEMDOCK docking tool. The final docking was done in AutoDock vina software. The ADMET properties of the selected ligands were done in admetSAR online server tool. The present study revealed that four derivatives of quercetin has excellent binding with Pantothenate Synthetase (PanC) of M. tuberculosis. These derivatives can be taken for in vitro enzymatic assays for its inhibitory property in the search for new anti-TB drugs.

scholarly journals Computational approach for the design of potential spike protein binding natural compounds in SARS- CoV2

2020 ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Protein Binding ◽  
Binding Site ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Cost Effective ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Novel Coronavirus

Abstract Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role as it is rapid, cost effective, compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus effected patients, in the present alarming situation. In this paper five phytochemicals which belong to flavonoid and anthraquinone subclass, selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. From the detail analysis of their molecular binding site on spike protein binding site with its receptor, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19.

scholarly journals Differential Effects of the Oncogenic BRAF Inhibitor PLX4032 (Vemurafenib) and its Progenitor PLX4720 on ABCB1 Function

2014 ◽  
Vol 17 (1) ◽  
pp. 154 ◽  
Author(s):  
Martin Michaelis ◽  
Florian Rothweiler ◽  
Thomas Nerreter ◽  
Marijke Van Rikxoort ◽  
Mohsen Sharifi ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Transport ◽  
Lentiviral Vector ◽  
3D Structure ◽  
Experimental Studies ◽  
Braf Inhibitor ◽  
Homology Model ◽  
Docking Study ◽  
Cellular Models ◽  
Culture Models

PURPOSE: The clinically approved oncogenic BRAF inhibitor PLX4032 (vemurafenib) was shown to be a substrate of the ATP-binding cassette (ABC) transporter ABCB1. Here, we compared PLX4032 and its structurally closely related precursor compound PLX4720 for their interference with ABCB1 and the ABCB1-mediated compound transport using docking and cell culture experiments. METHODS: For the docking study of PLX4032 and PLX4720 with ABCB1, we analysed binding of both compounds to mouse Abcb1a and to human ABCB1 using a homology model of human ABCB1 based on the 3D structure of Abcb1a. Naturally ABCB1 expressing cells including V600E BRAF-mutated and BRAF wild-type melanoma cells and cells transduced with a lentiviral vector encoding for ABCB1 were used as cell culture models. ABCB1 expression and function were studied by the use of fluorescent and cytotoxic ABCB1 substrates in combination with ABCB1 inhibitors. RESULTS: Docking experiments predicted PLX4032 to interact stronger with ABCB1 than PLX4720. Experimental studies using different cellular models and structurally different ABCB1 substrates confirmed that PLX4032 interfered stronger with ABCB1 function than PLX4720. For example, PLX4032 (20µM) induced a 4-fold enhanced rhodamine 123 accumulation compared to PLX4720 (20µM) in ABCB1-transduced UKF-NB-3 cells and reduced the IC50 for the cytotoxic ABCB1 substrate vincristine in this model by 21-fold in contrast to a 9-fold decrease induced by PLX4720. CONCLUSIONS: PLX4032 exerted stronger effects on ABCB1-mediated drug transport than PLX4720.  This indicates that small changes in a molecule can substantially modify its interaction with ABCB1, a promiscuous transporter that transports structurally different compounds.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.PURPOSE: The clinically approved oncogenic BRAF inhibitor PLX4032 (vemurafenib) was shown to be a substrate of the ATP-binding cassette (ABC) transporter ABCB1. Here, we compared PLX4032 and its structurally closely related precursor compound PLX4720 for their interference with ABCB1 and the ABCB1-mediated compound transport using docking and cell culture experiments. METHODS: For the docking study of PLX4032 and PLX4720 with ABCB1, we analysed binding of both compounds to mouse Abcb1a and to human ABCB1 using a homology model of human ABCB1 based on the 3D structure of Abcb1a. Naturally ABCB1 expressing cells including V600E BRAF-mutated and BRAF wild-type melanoma cells and cells transduced with a lentiviral vector encoding for ABCB1 were used as cell culture models. ABCB1 expression and function were studied by the use of fluorescent and cytotoxic ABCB1 substrates in combination with ABCB1 inhibitors. RESULTS: Docking experiments predicted PLX4032 to interact stronger with ABCB1 than PLX4720. Experimental studies using different cellular models and structurally different ABCB1 substrates confirmed that PLX4032 interfered stronger with ABCB1 function than PLX4720. For example, PLX4032 (20µM) induced a 4-fold enhanced rhodamine 123 accumulation compared to PLX4720 (20µM) in ABCB1-transduced UKF-NB-3 cells and reduced the IC50 for the cytotoxic ABCB1 substrate vincristine in this model by 21-fold in contrast to a 9-fold decrease induced by PLX4720. CONCLUSIONS: PLX4032 exerted stronger effects on ABCB1-mediated drug transport than PLX4720.  This indicates that small changes in a molecule can substantially modify its interaction with ABCB1, a promiscuous transporter that transports structurally different compounds. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Antiviral Activity ◽  
Binding Sites ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Docking Study ◽  
Spike Protein ◽  
Dimensional Structure ◽  
Molecular Docking Study

Abstract Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.

scholarly journals Computational approach for the design of potential spike protein binding natural compounds in SARS- CoV2

2020 ◽  
Author(s):  
Anamika Basu ◽  
Anasua Sarkar ◽  
Ujjwal Maulik
Keyword(s):  
Natural Products ◽  
Protein Binding ◽  
Binding Site ◽  
Transmembrane Protein ◽  
Experimental Studies ◽  
Cost Effective ◽  
Docking Study ◽  
Spike Protein ◽  
Molecular Docking Study ◽  
Novel Coronavirus

Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role as it is rapid, cost effective, compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus effected patients, in the present alarming situation. In this paper five phytochemicals which belong to flavonoid and anthraquinone subclass, selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. From the detail analysis of their molecular binding site on spike protein binding site with its receptor, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19.

scholarly journals GLYCOGEN SYNTHASE KINASE-3 BETA PROTEIN INHIBITION BY SELECTED PHYTOCOMPOUNDS IN SILICO

2016 ◽  
Vol 10 (1) ◽  
pp. 87
Author(s):  
Vanitha Varadharaj ◽  
Naresh Kandakatl
Keyword(s):  
Molecular Docking ◽  
Glycogen Synthase ◽  
Protein A ◽  
Experimental Studies ◽  
Docking Simulation ◽  
Docking Study ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Molecular Docking Study ◽  
Gsk 3Β

ABSTRACTObjectives: Bioactive phytocompounds are a rich source of chemopreventive substance. In the present investigation, docking study was performedfor the selected bioactive phytocompounds such as oleanolic acid, ecdysterone, betaine, stigmasterol acetate, and cinnamic acid to evaluate theiraffinity to glycogen synthase kinase-3 beta (GSK-3β) protein, a wound-healing biomarker. 2-chloro-5-[4-(3-chloro-phenyl)-2, 5-dioxo-2,5-dihydro-1hpyrrol-3-ylamino]-benzoicacid wasused as an inhibitorforGSK-3βwith minimum binding energy(−31.5 kcal/mol).Methods: Molecular docking study was conducted using AutoDock 4.2 version and the visualization result using Discover Studio 4.5.Results: The docking analysis ranked the selected phytocompounds that have high theoretical scores to bind to the proteins. The binding mode of thephytocompounds that bound to all the target proteins with high affinity was studied. The simulation demonstrated that the protein-ligand complexstabilized by multiple hydrogen bonds (H-bonds) was preferentially formed at the catalytic site. The results highlighted in this study reveals thatamong the selected lead phytocompounds that docked into the active site of GSK-3β, ecdysterone showed acceptable 6 H-bond interactions withresidues LYS85, TYR134, ARG141, GLN185, ASP200, PRO136 when compared to the reference compound with 5 H-bond interactions.Conclusion: Thus, based on the docking score ecdysterone could be considered as a novel compounds that can be used for experimental studies forthe inhibition of GSK-3β kinase. These results can be helpful for further design of novel GSK-3β inhibitors.Keywords: Phytocompounds, Molecular docking, Simulation, Receptor, Ligand, Inhibition.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

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