scholarly journals In Silico Docking Studies of Antimalarial Drug Hydroxychloroquine to SARS-CoV Proteins :An Emerging Pandemic Worldwide

2020 ◽  
Author(s):  
Priyanka H. Jokhakar ◽  
Rishee Kalaria ◽  
Hiren K. Patel
Keyword(s):  
Antimalarial Drug ◽  
Hydrophobic Interactions ◽  
Computational Study ◽  
Covalent Bond ◽  
Docking Studies ◽  
Protein Docking ◽  
Viral Attachment ◽  
Discovery Studio ◽  
In Silico Docking ◽  
Covalent Bond Formation

<p>This computational study comprises screening and prediction of interaction of selected antimalarial drug hydroxychloroquine with targeted two proteins of coronavirus. One is SARS enveloped E pantameric ion channel protein and another is SARS-CoV-2 main apoprotein protease. Both are vital for viral attachment and entry to the host cell for infection. After molecular protein docking with different confirmations, stable interacting complex of ligand and macromolecules were obtained. Interacting Lysine, Threonine and Tyrosine of E protein were found for participation of stable interaction with selected drug having docking affinity energy of -6.3kcal/mol. For apoprotein protease stable confirmation was screened out having bonding Threonine residue with same drug of energy -6.0 kcal/mol. Irreversible covalent bond formation and van der Waals interaction favours the selectivity and stability of both targeted proteins towards selected drug. Conventional as well as hydrophobic interactions are found in Ligplot and Discovery studio analysis also indicates stabilized confirmations between ligand and drug. Thus, this study delivers the putative mechanism of the drug interactions to target proteins hence comprising landmark for future investigation for antimalarial hydroxychloroquine as anti COVID 19 drug in this experimental time.</p>

scholarly journals In Silico Docking Studies of Antimalarial Drug Hydroxychloroquine to SARS-CoV Proteins :An Emerging Pandemic Worldwide

2020 ◽  
Author(s):  
Priyanka H. Jokhakar ◽  
Rishee Kalaria ◽  
Hiren K. Patel
Keyword(s):  
Antimalarial Drug ◽  
Hydrophobic Interactions ◽  
Computational Study ◽  
Covalent Bond ◽  
Docking Studies ◽  
Protein Docking ◽  
Viral Attachment ◽  
Discovery Studio ◽  
In Silico Docking ◽  
Covalent Bond Formation

<p>This computational study comprises screening and prediction of interaction of selected antimalarial drug hydroxychloroquine with targeted two proteins of coronavirus. One is SARS enveloped E pantameric ion channel protein and another is SARS-CoV-2 main apoprotein protease. Both are vital for viral attachment and entry to the host cell for infection. After molecular protein docking with different confirmations, stable interacting complex of ligand and macromolecules were obtained. Interacting Lysine, Threonine and Tyrosine of E protein were found for participation of stable interaction with selected drug having docking affinity energy of -6.3kcal/mol. For apoprotein protease stable confirmation was screened out having bonding Threonine residue with same drug of energy -6.0 kcal/mol. Irreversible covalent bond formation and van der Waals interaction favours the selectivity and stability of both targeted proteins towards selected drug. Conventional as well as hydrophobic interactions are found in Ligplot and Discovery studio analysis also indicates stabilized confirmations between ligand and drug. Thus, this study delivers the putative mechanism of the drug interactions to target proteins hence comprising landmark for future investigation for antimalarial hydroxychloroquine as anti COVID 19 drug in this experimental time.</p>

scholarly journals Molecular recognition of organic ammonium ions in solution using synthetic receptors

2010 ◽  
Vol 6 ◽  
Author(s):  
Andreas Späth ◽  
Burkhard König
Keyword(s):  
Molecular Recognition ◽  
Hydrophobic Interactions ◽  
Covalent Bond ◽  
Ammonium Ion ◽  
Synthetic Receptors ◽  
Ammonium Ions ◽  
Wide Range ◽  
Covalent Bond Formation ◽  
Reversible Covalent ◽  
Ion Receptors

Ammonium ions are ubiquitous in chemistry and molecular biology. Considerable efforts have been undertaken to develop synthetic receptors for their selective molecular recognition. The type of host compounds for organic ammonium ion binding span a wide range from crown ethers to calixarenes to metal complexes. Typical intermolecular interactions are hydrogen bonds, electrostatic and cation–π interactions, hydrophobic interactions or reversible covalent bond formation. In this review we discuss the different classes of synthetic receptors for organic ammonium ion recognition and illustrate the scope and limitations of each class with selected examples from the recent literature. The molecular recognition of ammonium ions in amino acids is included and the enantioselective binding of chiral ammonium ions by synthetic receptors is also covered. In our conclusion we compare the strengths and weaknesses of the different types of ammonium ion receptors which may help to select the best approach for specific applications.

scholarly journals Probing In Silico the Benzimidazole Privileged Scaffold for the Development of Drug-Like Anti-RSV Agents

2021 ◽  
Vol 14 (12) ◽  
pp. 1307
Author(s):  
Elena Cichero ◽  
Alessio Calautti ◽  
Valeria Francesconi ◽  
Michele Tonelli ◽  
Silvia Schenone ◽  
...  
Keyword(s):  
In Silico ◽  
Rational Design ◽  
Hydrophobic Interactions ◽  
Computational Study ◽  
Pharmacokinetic Profile ◽  
Careful Analysis ◽  
Docking Studies ◽  
F Protein ◽  
Privileged Scaffold ◽  
Orally Bioavailable

Targeting the fusion (F) protein has been recognized as a fruitful strategy for the development of anti-RSV agents. Despite the considerable efforts so far put into the development of RSV F protein inhibitors, the discovery of adequate therapeutics for the treatment of RSV infections is still awaiting a positive breakthrough. Several benzimidazole-containing derivatives have been discovered and evaluated in clinical trials, with only some of them being endowed with a promising pharmacokinetic profile. In this context, we applied a computational study based on a careful analysis of a number of X-ray crystallographic data of the RSV F protein, in the presence of different clinical candidates. A deepen comparison of the related electrostatic features and H-bonding motifs allowed us to pave the way for the following molecular dynamic simulation of JNJ-53718678 and then to perform docking studies of the in-house library of potent benzimidazole-containing anti-RSV agents. The results revealed not only the deep flexibility of the biological target but also the most relevant and recurring key contacts supporting the benzimidazole F protein inhibitor ability. Among them, several hydrophobic interactions and π-π stacking involving F140 and F488 proved to be mandatory, as well as H-bonding to D486. Specific requirements turning in RSV F protein binding ability were also explored thanks to structure-based pharmacophore analysis. Along with this, in silico prediction of absorption, distribution, metabolism, excretion (ADME) properties, and also of possible off-target events was performed. The results highlighted once more that the benzimidazole ring represents a privileged scaffold whose properties deserve to be further investigated for the rational design of novel and orally bioavailable anti-RSV agents.

scholarly journals Synthesis of Coumarins Linked With 1,2,3-Triazoles under Microwave Irradiation and Evaluation of their Antimicrobial and Antioxidant Activity

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Nibin Joy Muthipeedika ◽  
Yadav D Bodke ◽  
Sandeep Telkar ◽  
Vasily A Bakulev
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Antioxidant Properties ◽  
Cycloaddition Reaction ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
In Silico Docking ◽  
Antimicrobial And Antioxidant Activity ◽  
Plausible Reason

A series of coumarin derivatives linked with 1,2,3-triazoles has been synthesized by utilizing the copper catalyzed azide-alkyne cycloaddition reaction and were screened for their antimicrobial and antioxidant properties. Some of the compounds displayed promising antibacterial activities (MIC ranging from 5-150 µg/mL) and moderate antifungal activities as compared to the respective standards. The compounds 4k and 4g displayed good antibacterial activity when compared with the standard, Ciprofloxacin, and 4n exhibited better antifungal activity when compared to other synthesized compounds. The in silico docking studies of the active compounds were carried out against the gyrase enzyme and from those studies, it was acknowledged that 4k possessed significant hydrogen bonding and hydrophobic interactions which could be the plausible reason for its superior activity as compared to the other synthesized compounds. The compounds 4h and 4q showed promising antioxidant activity when compared with the standard, BHT, which could be attributed to the presence of electron donating substituents.                                                Resumen. Una serie de derivados de cumarina enlazados con 1,2,3-triazoles fue sintetizada empleando la reacción de cicloadición azida-alquino catalizada con cobre y fue evaluada en sus propiedades antimicrobianas y antioxidantes. Algunos de los compuestos exhibieron actividad antimicrobiana promisoria (intervalo MIC de 5-150 µg/mL) y actividad antifúngica moderada con respecto a los estándares respectivos. Los compuestos 4g y 4k mostraron buena actividad antibacterial con relación al estándar. Fluconazole y 4n exhibieron mejor actividad antifúngica en comparación con el resto de los compuestos. Se llevaron a cabo estudios in silico de modelado molecular e interacción de los compuestos activos con la enzima girasa ADN. De estos estudios se observó que 4k posee enlaces puentes de hidrógeno e interacciones hidrofóbicas significativos, los cuales podrían ser una causa plausible de su actividad mayor a aquélla mostrada por los otros compuestos sintetizados. Los compuestos 4h y 4q mostraron una importante actividad antioxidante comparada con el estándar (BHT), lo cual podría atribuirse a la presencia de sustituyentes electro-donadores

scholarly journals IN SILICO DOCKING ANALYSIS OF BIOACTIVE COMPOUNDS FROM CALOPHYLLUM INOPHYLLUM L. ETHANOL LEAF EXTRACT AGAINST EGFR PROTEIN

2017 ◽  
Vol 10 (8) ◽  
pp. 214 ◽  
Author(s):  
Jaikumar K ◽  
Sheik Noor Mohamed ◽  
John Wyson W ◽  
Deventhiran M ◽  
Babu A ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
In Silico ◽  
Leaf Extract ◽  
Growth Factor Receptor ◽  
Docking Studies ◽  
Docking Analysis ◽  
Calophyllum Inophyllum ◽  
Discovery Studio ◽  
In Silico Docking ◽  
Ms Analysis

Objective: The objective of this study was to evaluate the effective new phytocomponents from Calophyllum inophyllum ethanol leaf extract against breast cancer target protein of Epidermal Growth Factor Receptor (EGFR) using in silico docking studies.Materials and Methods: The identification of compounds was done by GC-MS analysis. The in silico docking studies were carried out using Discovery Studio 4.0 software.Results: The GC-MS analysis of ethanol leaf extract revealed the presence of eleven compounds. The docking analysis have exhibited moderate to potent inhibition with a range of dock score 3 to 55. 2H-Benzo(cd) pyrene-2,6(1,H)-dione, 3,5,7,10-tetrahydroxy-compound showed the dock score of 55.427.Conclusion: The results revealed out that the compounds present in Calophyllum inophyllum can inhibit the EGFR protein. The plant possesses anticancer potential because of the various bioactive compounds presence which is mainly responsible for anticancer activity. 

scholarly journals In Silico Docking Studies of Ag Nanoparticles and Its Derivatives Against NS5B Protein of Hepatitis-C Virus

2021 ◽  
Author(s):  
Arslan Akram ◽  
Waseem Ahmad ◽  
Muhammad Maaz Arif ◽  
Khaleeq Ahmad Saqib ◽  
Rameez-ul-Hassan Pirzada ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Silver Oxide ◽  
Docking Studies ◽  
Oxide Nanoparticles ◽  
Efficient Production ◽  
Computational Docking ◽  
Discovery Studio ◽  
In Silico Docking ◽  
Viable Systems ◽  
Silver Oxide Nanoparticles

Abstract Nanotechnology refers to the synthesis of nanomaterials (1-100nm) and their applications. Nanoscience can deal with individual atoms and molecules. In recent times, an agreement has started to rise about the informatics foundation expected to accumulate, curate, and share data among every one of the fields in nanotechnology. Nanoinformatics is fulfilling this demand. It is the science about figuring out which data is important to the nanoscale science and after that creating and implementing viable systems for gathering, approving, sharing, analyzing, modeling, and applying that information. Nanoinformatics is essential for efficient production and relative description of nanomaterials. The present study focused on the prediction of interactions of three ligands i.e. silver nanoparticles, tyrosine capped silver nanoparticles, and silver oxide nanoparticles with NS5B protein of HCV. ΑutoDock 4, Discovery Studio, ChemDraw Ultra, OpenBabel, and Chimera software were used. Computational docking helps to evaluate conformations of small ligands attached to macromolecular proteins. NS5B plays a crucial role in HCV replication. It weighs about 66-KDa. It is an RNA-dependent RNA membrane-associated polymerase. The results were obtained from AutoDock 4 and visualized in Discovery Studio and Chimera. Silver nanoparticles showed interactions with LYS81, LYS172, LYS173, TYR176, and ASP177. Tyrosine capped silver nanoparticles formed bonds with SER218, ASP220, GLU357, and LEU362 in the palm region. Silver oxide nanoparticles interacted with LEU260, TYR261, ARG280, and ALA281 in the finger domain. All these three ligands showed promising results to inhibit the NS5B enzyme halting HCV replication.

scholarly journals Systematic Analysis of Compounds Present in Ocimum Tenuiflorum (Tulsi) Regarding its Anti-Inflammatory Properties Using In-Silico Techniques

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Jinay Patel ◽  
Sonia Arora
Keyword(s):  
In Silico ◽  
Literature Search ◽  
Data Bank ◽  
Docking Studies ◽  
Systematic Analysis ◽  
Discovery Studio ◽  
In Silico Docking ◽  
Chemical Structures ◽  
Ocimum Tenuiflorum ◽  
Anti Inflammatory

The objective of this study was to gather data, create a database of the compounds present in Ocimum tenuiflorum (O. tenuiflorum), and gather related literature on the compounds found. A thor-ough literature search was performed to gather in-formation on compounds present in O. tenuiflorum, including chemical structures, relative abundance, presence in different plant parts, and availability from chemical supply vendors. The compounds’ chemical structures were refined using Discovery Studio Visualizer and Chimera software for future in-silico docking studies. The structures with cleaned structural geometry were obtained through D.S. Vis-ualizer for docking in the future. From the literature search of previously presented articles, it was found that methyl eugenol had the greatest percent com-position in O. tenuiflorum. After searching the Pro-tein Data Bank, COX-1, COX-2, and NF Kappa B were found to be the main protein targets of O. ten-uiflorum compounds in the arachidonic acid inflamematory pathway. Thus, the anti-inflammatory proper-ties of O. tenuiflorum have been analyzed in this ar-ticle for future in silico docking.

COMPUTATIONAL ANALYSIS OF NARINGENIN AS AN ANTIDEPRESSANT

2020 ◽  
pp. 109-112
Author(s):  
PREMJANU N ◽  
CHELLAM JAYNTHY
Keyword(s):  
Computational Analysis ◽  
Antioxidant Activities ◽  
Computational Study ◽  
Promising Result ◽  
Antidepressant Drug ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Studies ◽  
Neuroprotective Effects ◽  
Discovery Studio

Objective: This works aims at analyzing the potential of Naringenin (NAR) as an antidepressant drug by computational methods. Methods: The database Protein Data Bank and PubChem were used to retrieve the three-dimensional structures of the protein and the compound. The software Discovery Studio was used to study the interactions between the protein and the ligand. Results: NAR, one of the flavanone, which has strong anti-inflammatory and antioxidant activities, is studied for its antidepressant and neuroprotective effects through in silico approach. Interaction study and pharmacophore analysis using Discovery Studio show that the molecule NAR interacts with the protein at different sites. The interaction has a maximum dock score at position B. Conclusion: The compound NAR shows to have antidepressant quality from the computational study. The docking studies show promising result that NAR can be explored further as a potential drug.

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes

2020 ◽  
Vol 17 (2) ◽  
pp. 233-247
Author(s):  
Krishna A. Gajjar ◽  
Anuradha K. Gajjar
Keyword(s):  
Molecular Docking ◽  
Structural Information ◽  
Docking Studies ◽  
Structural Motif ◽  
Roc Curve Analysis ◽  
Ligand Complex ◽  
Discovery Studio ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Pharmacophore Models

Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Results and Conclusion: Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.

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