Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibits P38 Protein: Probable Remedies for Hepatocellular Carcinoma

2020 ◽  
Vol 16 (3) ◽  
pp. 350-357
Author(s):  
Heena Tabassum ◽  
Iffat Z. Ahmad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Docking ◽  
Binding Energy ◽  
Simulation Analysis ◽  
Nigella Sativa ◽  
Pharmacological Action ◽  
Dynamics Simulation ◽  
Ligand Interaction ◽  
Lipinski’S Rule ◽  
Discovery Studio

Background: Currently, a novel antagonist against p38 is being designed and applied to inhibit hepatocellular carcinoma. Protein–ligand interaction plays a major role in the identification of the possible mechanism for the pharmacological action. The involvement of p38 remains an important target for anticancer drug development as its activation induces apoptosis in hepatoma cells. Objective: The aim is to identify the best candidate from the plants of N. sativa which binds with the hepatocellular carcinoma (HCC) targets by computational approach. Materials and Methods: The reported phytoconstituents such as thymoquinone and thymol present in the plant, N. sativa were docked with the HCC target such as p38. Structures of phytoconstituents were prepared using ChemDraw Ultra 10 software and converted into its 3D PDB structure and minimized using Discovery Studio client 2.5. The target protein, p38 was retrieved from RCSB PDB. Lipinski’s rule and ADMET toxicity profiling were carried out on the phytoconstituents of the N. sativa, and the compounds were further promoted for molecular docking and MD simulation analysis. Results: The docking results revealed promising inhibitory potential of thymoquinone against p38 with binding energy of -7.67 kcal/mole as compared to its known standard doxorubicin having binding energy of -6.68 kcal/mol respectively. Further, molecular dynamic (MD) simulations for 5ns were conducted for optimization, flexibility prediction, and determination of folded p38 stability. The p38-thymoquinone complex was found to be quite stable with RMSD value of 0.2 nm. Conclusion: Obtained results propose thymoquinone binding energy on the selected targets. Hence, this compound bears outstanding potential against hepatocellular carcinoma and has to be taken up for experimental work against hepatocellular carcinoma.

scholarly journals Exploring the Potency of Nigella sativa Seed in Inhibiting SARS-CoV-2 Main Protease Using Molecular Docking and Molecular Dynamics Simulations

2021 ◽  
Vol 21 (5) ◽  
pp. 1252
Author(s):  
Ari Hardianto ◽  
Muhammad Yusuf ◽  
Ika Wiani Hidayat ◽  
Safri Ishmayana ◽  
Ukun Mochammad Syukur Soedjanaatmadja
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Global Economy ◽  
Nigella Sativa ◽  
Scientific Information ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Main Protease ◽  
Dynamics Simulations

Coronavirus disease (COVID-19) is a pandemic burdening the global economy. It is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Black cumin (Nigella sativa) seed may contain antivirals for the disease since it was reported to inhibit the human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Main protease (Mpro) is a vital protein for viral replication and a promising target for COVID-19 drug development. Hence, in this study, we intended to uncover the potency of N. sativa seed as the natural source of inhibitors for SARS-CoV-2 Mpro. We collected secondary metabolites in N. sativa seed through a literature search and employed Lipinski’s rule of five as the initial filter. Subsequently, virtual screening campaigns using a molecular docking method were performed, with N3 inhibitor and leupeptin as reference ligands. The top hits were analyzed further using a molecular dynamics simulation approach. Molecular dynamics simulations showed that binding affinities of nigellamine A2 and A3 to Mpro are comparable to that of leupeptin, with median values of -43.9 and -36.2 kcal mol–1, respectively. Ultimately, this study provides scientific information regarding N. sativa seeds’ potency against COVID-19 and helps direct further wet experiments.

scholarly journals Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis

2021 ◽  
Vol 14 (4) ◽  
pp. 357
Author(s):  
Magdi E. A. Zaki ◽  
Sami A. Al-Hussain ◽  
Vijay H. Masand ◽  
Siddhartha Akasapu ◽  
Sumit O. Bajaj ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Simulation Analysis ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Dynamics Simulation ◽  
Multilinear Regression ◽  
Qsar Analysis ◽  
Main Protease

Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

scholarly journals Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2071
Author(s):  
Syed Sayeed Ahmad ◽  
Meetali Sinha ◽  
Khurshid Ahmad ◽  
Mohammad Khalid ◽  
Inho Choi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Md Simulation ◽  
Simulation Analysis ◽  
Dynamics Simulation ◽  
Caspase 8 ◽  
Amino Acid Residues ◽  
The Stability ◽  
Molecular Docking And Dynamics

Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.

Advancements in Docking and Molecular Dynamics Simulations Towards Ligand-receptor Interactions and Structure-function Relationships

2018 ◽  
Vol 18 (20) ◽  
pp. 1755-1768 ◽  
Author(s):  
Ahmad Abu Turab Naqvi ◽  
Taj Mohammad ◽  
Gulam Mustafa Hasan ◽  
Md. Imtaiyaz Hassan
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Drug Discovery ◽  
Molecular Dynamics Simulations ◽  
Computational Method ◽  
Dynamics Simulation ◽  
Ligand Molecule ◽  
Ligand Interaction ◽  
Modern Drug ◽  
Dynamics Simulations

Protein-ligand interaction is an imperative subject in structure-based drug design and protein function prediction process. Molecular docking is a computational method which predicts the binding of a ligand molecule to the particular receptor. It predicts the binding pose, strength and binding affinity of the molecules using various scoring functions. Molecular docking and molecular dynamics simulations are widely used in combination to predict the binding modes, binding affinities and stability of different protein-ligand systems. With advancements in algorithms and computational power, molecular dynamics simulation is now a fundamental tool to investigative bio-molecular assemblies at atomic level. These methods in association with experimental support have been of great value in modern drug discovery and development. Nowadays, it has become an increasingly significant method in drug discovery process. In this review, we focus on protein-ligand interactions using molecular docking, virtual screening and molecular dynamics simulations. Here, we cover an overview of the available methods for molecular docking and molecular dynamics simulations, and their advancement and applications in the area of modern drug discovery. The available docking software and their advancement including application examples of different approaches for drug discovery are also discussed. We have also introduced the physicochemical foundations of molecular docking and simulations, mainly from the perception of bio-molecular interactions.

scholarly journals Molecular Docking and Dynamics Simulation Studies Predict Munc18b as a Target of Mycolactone: A Plausible Mechanism for Granule Exocytosis Impairment in Buruli Ulcer Pathogenesis

Toxins ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 181 ◽  
Author(s):  
Samuel Kwofie ◽  
Bismark Dankwa ◽  
Kweku Enninful ◽  
Courage Adobor ◽  
Emmanuel Broni ◽  
...  
Keyword(s):  
Wound Healing ◽  
Molecular Docking ◽  
Mast Cells ◽  
Binding Energy ◽  
Buruli Ulcer ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Granule Exocytosis ◽  
Molecular Docking Studies ◽  
Healing Processes

Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin. Wound healing processes involve activation of the blood platelets to release the contents of the dense granules mainly serotonin, calcium ions, and ADP/ATP by exocytosis into the bloodstream. The serotonin release results in attracting more platelets and mast cells to the wound site, with the mast cells also undergoing degranulation, releasing compounds into the bloodstream by exocytosis. Recent work has identified interference in the co-translational translocation of many secreted proteins via the endoplasmic reticulum and cell death involving Wiskott-Aldrich syndrome protein (WASP), Sec61, and angiotensin II receptors (AT2R). We hypothesized that mycolactone by being lipophilic, passively crosses cell membranes and binds to key proteins that are involved in exocytosis by platelets and mast cells, thus inhibiting the initiation of wound healing processes. Based on this, molecular docking studies were performed with mycolactone against key soluble n-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and regulators, namely Vesicle-associated membrane protein (VAMP8), Synaptosomal-associated protein (SNAP23, syntaxin 11, Munc13-4 (its isoform Munc13-1 was used), and Munc18b; and also against known mycolactone targets (Sec61, AT2R, and WASP). Munc18b was shown to be a plausible mycolactone target after the molecular docking studies with binding affinity of −8.5 kcal/mol. Structural studies and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding energy calculations of the mycolactone and Munc18b complex was done with 100 ns molecular dynamics simulations using GROMACS. Mycolactone binds strongly to Munc18b with an average binding energy of −247.571 ± 37.471 kJ/mol, and its presence elicits changes in the structural conformation of the protein. Analysis of the binding interactions also shows that mycolactone interacts with Arg405, which is an important residue of Munc18b, whose mutation could result in impaired granule exocytosis. These findings consolidate the possibility that Munc18b could be a target of mycolactone. The implication of the interaction can be experimentally evaluated to further understand its role in granule exocytosis impairment in Buruli ulcer.

scholarly journals Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Chandrabhan Seniya ◽  
Ghulam Jilani Khan ◽  
Kuldeep Uchadia
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Secondary Metabolite ◽  
Therapeutic Potential ◽  
Dynamics Simulation ◽  
Cholinesterase Inhibition ◽  
Ligand Molecule ◽  
Ligand Interaction ◽  
Dynamics Simulations

Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer’s dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite fromCannabisplant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration ofC28H34N2O6as a valuable small ligand molecule in treatment and prevention of AD associated disorders and furtherin vitroandin vivoinvestigations may prove its therapeutic potential.

scholarly journals Ligand Based 3D-QSAR Pharmacophore, Molecular Docking and Adme to Identify Potential Fibroblast Growth Factor Receptor 1 Inhibitors 

2020 ◽  
Author(s):  
Zizhong Tang ◽  
Lu Huang ◽  
Xiaoli Fu ◽  
Haoxiang Wang ◽  
Biao Tang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Growth Factor Receptor ◽  
Pharmacophore Model ◽  
3D Qsar ◽  
Drug Carriers ◽  
Therapeutic Effects ◽  
Lipinski’S Rule ◽  
Discovery Studio ◽  
Zinc Database

Abstract The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Twenty-one known inhibitors were collected as training sets to establish a 3D-QSAR pharmacophore model, and cost analysis, test set validation, and Fischer randomization test were used to validate the efficiency of the pharmacophore model. In Accelrys Discovery Studio 2016, the zinc database was filtered by Lipinski's Rule of Five and SMART's filtration. Then, Hypo01 was used for virtual screening of ZINC database. Compounds with predicted activity values less than 1 μM were molecularly docked with FGFR1 protein crystals, the docking results were observed, and the interaction between compounds and targets was studied. The absorption, distribution, metabolism and excretion (ADME) and toxicity of potential inhibitors were studied, and a compound with new structural scaffolds were obtained. It could be further studied to explore their better therapeutic effects.

scholarly journals An In silico Analysis of Some Bioactive Compounds of Psidium guajava against Target Proteins of Vibrio cholerae

2020 ◽  
pp. 14-24
Author(s):  
Yakubu Gambo Hamza ◽  
Aminu Ibrahim Danyaya ◽  
Mudassir Lawal
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Vibrio Cholerae ◽  
Bioactive Compounds ◽  
Psidium Guajava ◽  
The Body ◽  
In Vivo Studies ◽  
Watery Diarrhea ◽  
Ligand Interaction ◽  
Acute Watery Diarrhea

Introduction: Cholera is a destructive disease that causes extreme and intense water loss in the body. It takes between 12 hours and 5 days for an individual to show symptoms after ingesting contaminated food or water. It causes acute watery diarrhea in children and adults and if left untreated, it can lead to death within hours. Unfortunately, children are the most severely affected. In this study, molecular interactions of 24 bioactive compounds of Psidium guajava leaves against Vibrio cholerae targets proteins namely: Alanine racemase (PDB ID: 4BEQ), Cholera enterotoxin, A chain (PDB ID: 1S5F) and ToxT (PDB ID: 3GBG) were evaluated. Methods: Molecular docking study was conducted and the 3D structures of bioactive compounds, Enzymes and the Enzyme-ligand interaction were visualized while Swiss ADME was employed to assess other physiochemical properties of these bioactive compounds. Results and Discussion: The results from the molecular docking revealed that five bioactive compounds showed promising inhibitory activity, which include Spathulenol (Binding energy; -7.5, -6.5 and -9.1 kcal/mol in 4BEQ, 1S5F and 3GBG ), Humulene oxide II (Binding energy; -7.1, -6.0 and -8.5 kcal/mol in 4BEQ, 1S5F and 3GBG), Globulol(-)-Globulol were -7.2, -6.5 and -9.0 kcal/mol in 4BEQ, 1S5F and 3GBG), Cadala-1(10),3,8-triene (Binding energy; -7.8, -6.8 and -9.8 kcal/mol in 4BEQ, 1S5F and 3GBG) and Bicyclo[5.3.0]decane, 2-methylene-5-(1-methylvinyl)-8-methyl (Binding energy; -6.9, -6.7 and -9.4 kcal/mol in 4BEQ, 1S5F and 3GBG) respectively. Conclusion: In this study, it has been revealed that the carefully chosen bioactive compounds have the potential to be used alone or in combination with other natural products for developing potent antibacterial drugs (against cholera). They can be further subjected to fractionation and isolation to confirm their activity towards in vitro and in vivo studies and can be commercialized as a potent antibacterial agent.

scholarly journals MOLECULAR DOCKING STUDY OF NATURALLY OCCURRING COMPOUNDS AS INHIBITORS OF COVID -19

2021 ◽  
pp. 69-71
Author(s):  
SREEDEVI A ◽  
MALAR RETNA A ◽  
ROBIN KUMAR SAMUEL
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Discovery Studio ◽  
Naturally Occurring ◽  
Short Period ◽  
The Right ◽  
Native Ligand ◽  
Made In

Objectives: The worldwide spread of COVID-19 is an emergent issue to be tackled. Currently, several works in various field have been made in rather short period. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors using molecular docking study. Methods: The docking analyses were performed by using Autodock, Discovery Studio Visualiser and Igemdock. Results: The binding energy obtained from the docking of 6LU7 with native ligand cupressuflavone is -8.9 kcal/mol. Conclusion: These findings will provide the opportunities to identify the right drug to combat COVID-19.

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