scholarly journals IN SILICO AND MOLECULAR DYNAMIC STUDIES OF NATURAL FLAVONOIDS FOR THEIR INHIBITORY PATTERN AGAINST INTERLEUKIN-6 (1ALU) AND TNF-Α (5MU8) FOR MANAGEMENT OF ULCERATIVE COLITIS

2021 ◽  
Vol 10 (6) ◽  
pp. 3766-3773
Author(s):  
Manish Kumar Gupta
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Interleukin 6 ◽  
Dynamic Studies ◽  
Starting Point ◽  
Tnf Α ◽  
Ancient Times ◽  
Dynamics Modelling

The search for a prospective lead chemical is a time-consuming and complicated procedure that necessitates a lot of money, patience, and labour. Humans have been using phytochemicals, especially secondary metabolites, for this purpose since ancient times, and they are still on the hunt for even source for drug discovery. Natural flavonoids including rhamnetin, eupatorin, and primuletin are involved in the treatment of numerous biological diseases. The research focuses on molecular docking of 10 flavonoid compounds with the Interleukin-6 (1ALU) and TNF-α (5MU8) to assess the binding affinity at the binding location with the highest binding affinity. The flavonoid-protein complex with the highest binding affinity and interactions was studied using molecular dynamics modelling. With the Interleukin-6 (1ALU) and TNF-α (5MU8), the flavonoid naringin had the lowermost binding energy of 9.8 Kcal/mol. It took 20 nanoseconds to complete and yielded satisfactory results. The rhamnetin, eupatorin, and primuletin residues are more successful at maintaining flavonoid stability against Interleukin-6 (1ALU) and TNF-α (5MU8), according to the overall results of our simulation. These expected results will serve as a starting point for more investigation into the significance of their drug-likeliness properties in the management of ulcerative colitis.

scholarly journals Molecular Docking and Molecular Dynamics Simulation Studies of Triterpenes from Vernonia patula with the Cannabinoid Type 1 Receptor

2021 ◽  
Vol 22 (7) ◽  
pp. 3595
Author(s):  
Md Afjalus Afjalus Siraj ◽  
Md. Sajjadur Rahman ◽  
Ghee T. Tan ◽  
Veronique Seidel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Cannabinoid Type 1 Receptor ◽  
Docking Approach

A molecular docking approach was employed to evaluate the binding affinity of six triterpenes, namely epifriedelanol, friedelin, α-amyrin, α-amyrin acetate, β-amyrin acetate, and bauerenyl acetate, towards the cannabinoid type 1 receptor (CB1). Molecular docking studies showed that friedelin, α-amyrin, and epifriedelanol had the strongest binding affinity towards CB1. Molecular dynamics simulation studies revealed that friedelin and α-amyrin engaged in stable non-bonding interactions by binding to a pocket close to the active site on the surface of the CB1 target protein. The studied triterpenes showed a good capacity to penetrate the blood–brain barrier. These results help to provide some evidence to justify, at least in part, the previously reported antinociceptive and sedative properties of Vernonia patula.

scholarly journals Identification of Potent Inhibitors against Aurora Kinase A Using Molecular Docking and Molecular Dynamics Simulation Studies

2019 ◽  
Author(s):  
Sathishkumar Chinnasamy ◽  
Gurudeeban Selvaraj ◽  
Aman Chandra Kaushik ◽  
Satyavani Kaliamurthi ◽  
Asma Sindhoo Nangraj ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Affinity ◽  
Aurora Kinase ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Aurora Kinase A ◽  
High Binding Affinity ◽  
Kinase A

Aurora kinase A (AURKA) is a normal cell proliferation-inducing enzyme encoded by AURKA gene, with over-expression observed in different types of malignancies. Hence, the goal is to find potential inhibitors against AURKA. In this study, molecular docking, Standard Precision and Extra Precision methods were employed. After the docking study, the ligands showed an extremely low binding score which suggested very high binding affinity of the ligands. Furthermore, Quantum polarized ligand docking (QPLD) was performed to predict the binding status of the molecules. Based on the binding affinity, the top four compounds were chosen for further analysis. The docked complexes were further analyzed in explicit water conditions using 100 ns molecular dynamics simulations and binding free energy calculation. Then, density functional theory (DFT) calculation was used to calculate the molecular properties of the molecules. Finally, systems biology experiments validated the molecular docking and molecular dynamics simulation studies and indicated that quercetin, kaempferol, luteolin and rutin could inhibit the AURKA. The results show that, these four molecules have high binding affinity to the AURKA and significant interactions (LEU139, GLU211and ALA213) were also identified with the hinge region of Aurora kinase A. Thus, LEU139, GLU211, and ALA213 were identified as the crucial protein mechanisms.

scholarly journals Molecular Docking and Molecular Dynamics Studies on Selective Synthesis of α-Amyrin and β-Amyrin by Oxidosqualene Cyclases from Ilex Asprella

2019 ◽  
Vol 20 (14) ◽  
pp. 3469 ◽  
Author(s):  
Zhixue Wu ◽  
Hui Xu ◽  
Meiling Wang ◽  
Ruoting Zhan ◽  
Weiwen Chen ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Protein Structures ◽  
Free Energy Calculations ◽  
Selective Synthesis ◽  
Total Production ◽  
Oxidosqualene Cyclases ◽  
Free Energy Decomposition

Amyrins are the immediate precursors of many pharmaceutically important pentacyclic triterpenoids. Although various amyrin synthases have been identified, little is known about the relationship between protein structures and the constituent and content of the products. IaAS1 and IaAS2 identified from Ilex asprella in our previous work belong to multifunctional oxidosqualene cyclases and can produce α-amyrin and β-amyrin at different ratios. More than 80% of total production of IaAS1 is α-amyrin; while IaAS2 mainly produces β-amyrin with a yield of 95%. Here, we present a molecular modeling approach to explore the underlying mechanism for selective synthesis. The structures of IaAS1 and IaAS2 were constructed by homology modeling, and were evaluated by Ramachandran Plot and Verify 3D program. The enzyme-product conformations generated by molecular docking indicated that ASP484 residue plays an important role in the catalytic process; and TRP611 residue of IaAS2 had interaction with β-amyrin through π–σ interaction. MM/GBSA binding free energy calculations and free energy decomposition after 50 ns molecular dynamics simulations were performed. The binding affinity between the main product and corresponding enzyme was higher than that of the by-product. Conserved amino acid residues such as TRP257; TYR259; PHE47; TRP534; TRP612; and TYR728 for IaAS1 (TRP257; TYR259; PHE473; TRP533; TRP611; and TYR727 for IaAS2) had strong interactions with both products. GLN450 and LYS372 had negative contribution to binding affinity between α-amyrin or β-amyrin and IaAS1. LYS372 and ARG261 had strong repulsive effects for the binding of α-amyrin with IaAS2. The importance of Lys372 and TRP612 of IaAS1, and Lys372 and TRP611 of IaAS2, for synthesizing amyrins were confirmed by site-directed mutagenesis. The different patterns of residue–product interactions is the cause for the difference in the yields of two products.

scholarly journals Remdesivir Strongly Binds to both RNA-dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations

2020 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Thai Nguyen ◽  
Duc Toan Truong ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Recent Experiment ◽  
Umbrella Sampling ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
The World ◽  
Binding Mechanisms

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome–<br>coronavirus 2) has caused a global CoVid-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for CoVid-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, Remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to CoVid-19 patients in many countries. A recent experiment showed that Remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics and umbrella sampling we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that Remdesivir binds to Mpro slightly weaker than to RdRp and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of<br>Remdesivir to two targets differ in that electrostatic interaction is the main force in stabilizing the RdRp-Remdesivir complex, while the van der Waals interaction dominates in the MproRemdesivir case. Our result indicates that Remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating Covid-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease. <br>

scholarly journals Hepatoprotective Activity of Pirdot Leaves (Saurauia vulcani Korth) Ethanol Extract in Laboratory Rats (Rattus norvegicus) and Characterization of Bioactive Compounds Using a Molecular Docking Approach

2021 ◽  
Vol 9 (A) ◽  
pp. 1265-1270
Author(s):  
Erlintan Sinaga ◽  
Syafruddin Ilyas ◽  
Salomo Hutahaean ◽  
Panal Sitorus
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Bioactive Compounds ◽  
Ethanol Extract ◽  
Treated Group ◽  
Hepatoprotective Activity ◽  
Tnf Α ◽  
Pomolic Acid ◽  
Docking Approach ◽  
Cox 2

AIM: The hepatoprotective activities of  bioactive compounds Pirdot were investigated in vivo and in silico. METHODS: In this study, the completely randomized design non-factorial was experimentally to assess the value of SGPT and SGOT and twenty four adult male rats were divided into four groups : group G0, control group; group G1, a treated group received 0.1 ml sheep red blood cell; group G2, a treated group received 500 mg ethanol extract Pirdot; group G3, a group treated received 500 mg ethanol extract Pirdot and 0,1 ml sheep red blood cell. On thirty one days of treatment, the blood of all rats group were taken to value SGPT and SGOT using DiaLab kit. Furthermore, the molecular docking study was done to analyse molecular interaction that COX-2 and  TNF-α were the primary target protein of bioactive compounds of Pirdot associated with hepatoprotective activities. In addition, it tends to be the target of non-steroidal anti-inflammatory drugs such as Ibuprofen. RESULTS: The results show SGOT and SGPT value significantly [p<0.05] decreased on Group G2 and G3. Moreover, the bioactive compounds of Pirdot, such as Pomolic acid and Ursolic acid tend to be the potential compound on liver protection. Moreover, Pomolic acid has a good binding affinity -14.6 kcal mol-1 with COX-2 Protein and the binding affinity of cis-3-O-p-hydroxycinnamoyl Ursolic acid was -15.1 kcal mol-1 associated with TNF-α Protein. CONLUSION:  Pirdot Leaves (Saurauia vulcani Korth.)  Ethanol Extract showed Hepatoprotective activity in rats (Rattus norvegicus). Molecular docking approach showed that pomolic acid has a good binding affinity with COX-2 Protein and TNF-α Protein.

scholarly journals Network pharmacology for the identification of phytochemicals in traditional Chinese medicine for COVID-19 that may regulate interleukin-6

2020 ◽  
Author(s):  
Chun Liang ◽  
Wenhao Niu ◽  
Feng Wu ◽  
Wenyue Cao ◽  
Zonggui Wu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Binding Affinity ◽  
Ursolic Acid ◽  
Interleukin 6 ◽  
Chemical Constituents ◽  
Gene Clusters ◽  
Network Pharmacology ◽  
Biological Processes

Objective: “Three formulas and three medicines,” namely, Jinhua Qinggan Granule, Lianhua Qingwen Capsule, Xuebijing Injection, Qingfei Paidu Decoction, HuaShi BaiDu Formula, and XuanFei BaiDu Granule, were proven to be effective for coronavirus disease 2019 (COVID-19) treatment. This study aimed to identify the active chemical constituents of this traditional Chinese medicine (TCM) and investigate their mechanisms through interleukin-6 (IL-6) integrating network pharmacological approaches.Methods: We collected the compounds from all herbal ingredients of the previously mentioned TCM, but those that could downregulate IL-6 were screened through the network pharmacology approach. Then, we modeled molecular docking to evaluate the binding affinity between compounds and IL-6. Furthermore, we analyzed the biological processes and pathways of compounds. Lastly, we screened out the core genes of compounds through the construction of the protein-protein interaction network and the excavation of gene clusters of compounds.Results: The network pharmacology research showed that TCM could decrease IL-6 using several compounds, such as quercetin, ursolic acid, luteolin, and rutin. Molecular docking results showed that the molecular binding affinity with IL-6 of all compounds except γ-aminobutyric acid was &lt; −5.0 kJ/mol, indicating the potential of numerous active compounds in TCM to directly interact with IL-6, leading to an anti-inflammation effect. Finally, Cytoscape 3.7.2 was used to topologize the biological processes and pathways of compounds, revealing potential mechanisms for COVID-19 treatment.Conclusion: These results indicated the positive effect of TCM on the prevention and rehabilitation of COVID-19 in at-risk people. Quercetin, ursolic acid, luteolin, and rutin could inhibit COVID-19 by downregulating IL-6.

scholarly journals In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaolu Liu ◽  
Yuling Fan ◽  
Lipeng Du ◽  
Zhigang Mei ◽  
Yang Fu
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Chronic Inflammatory Bowel Disease ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Tnf Α

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6.

scholarly journals Comparison of Molecular Docking and Molecular Dynamics Simulations of 1,3-Thiazin-4-One with MDM2 Protein

2015 ◽  
Vol 60 ◽  
pp. 161-167 ◽  
Author(s):  
S. Athavan Alias Anand ◽  
C. Loganathan ◽  
K. Saravanan ◽  
S. Kabilan
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Binding Modes ◽  
Software Suite ◽  
Mdm2 Protein ◽  
Important Amino Acid ◽  
Dynamic Studies ◽  
Dynamics Simulations ◽  
Oncogene Protein

The molecular docking and molecular dynamics simulations studies of 1,3–thiazin–4–one derivative with a bonafide oncogene protein MDM2 (PDB ID: 4HBM) was investigated. Both the docking and dynamics simulations were performed in Schrödinger software suite 2014 using Glide and Desmond modules. The results of docking and dynamics were compared to investigate the possible binding modes of the thiazinone derivative with 4HBM. The tested molecule shows critical interactions with the important amino acid His 96 which is necessary for the inhibition of MDM2 in both docking and dynamic studies.

scholarly journals Remdesivir Strongly Binds to both RNA-dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations

2020 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Thai Nguyen ◽  
Duc Toan Truong ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rna Polymerase ◽  
Binding Affinity ◽  
Recent Experiment ◽  
Umbrella Sampling ◽  
Rna Dependent Rna Polymerase ◽  
Main Protease ◽  
The World ◽  
Binding Mechanisms

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome–<br>coronavirus 2) has caused a global CoVid-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for CoVid-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, Remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to CoVid-19 patients in many countries. A recent experiment showed that Remdesivir binds to SARS-CoV-2 with an inhibition constant of μM, but the exact target has not been reported. In this work, combining molecular docking, steered molecular dynamics and umbrella sampling we examined its binding affinity to two targets including the main protease (Mpro), also known as 3C-like protease, and RdRp. We showed that Remdesivir binds to Mpro slightly weaker than to RdRp and the corresponding inhibition constants, consistent with the experiment, fall to the μM range. The binding mechanisms of<br>Remdesivir to two targets differ in that electrostatic interaction is the main force in stabilizing the RdRp-Remdesivir complex, while the van der Waals interaction dominates in the MproRemdesivir case. Our result indicates that Remdesivir can target not only RdRp but also Mpro, which can be invoked to explain why this drug is effective in treating Covid-19. We have identified residues of the target protein that make the most important contribution to binding affinity, and this information is useful for drug development for this disease. <br>

scholarly journals MOLECULAR DYNAMIC SIMULATION OF ASIATIC ACID DERIVATIVES COMPLEX WITH INDUCIBLE NITRIC OXIDE SYNTHASE ENZYME AS AN ANTI-INFLAMMATORY

2021 ◽  
pp. 32-38
Author(s):  
IDA MUSFIROH ◽  
HANIFAHZIN KHATAMI ◽  
SANDRA MEGANTARA ◽  
MUCHTARIDI MUCHTARIDI
Keyword(s):  
Nitric Oxide ◽  
Molecular Dynamics ◽  
Molecular Docking ◽  
Nitric Oxide Synthase ◽  
Binding Affinity ◽  
Inducible Nitric Oxide Synthase ◽  
Asiatic Acid ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Objective: The aim of this study was to determine the stability interaction of asiatic acid derivatives (AA) complex with inducible nitric oxide synthase (iNOS) enzyme as an anti-inflammatory using Molecular Dynamic (MD) simulation. Methods: The methods were consisting of validation of molecular docking, molecular docking to calculate binding affinity within the complex between the compounds and iNOS enzyme by using MMGBSA (Molecular Mechanics/Generalized Born Surface Area), and MD system preparation, MD production as well as MD analysis using AMBER18. Results: The result of validation and molecular docking were AA5 has the most negative Gibbs energy that is -9.17 kcal/mol, which has better binding affinity than other derivatives than other derivatives. The molecular dynamics simulation of the modified structure of asiatic acid showed that binding energy value and RMSD of AA5, AA6 and AA9 have a lower value compared to arginine as a substrate of iNOS enzyme. Molecular Dynamics that have been occurred to the best three compounds chosen shown good result in terms of stability after 100 ns length simulation. And the lowest binding affinity has been achieved by a compound called AA5. Out of all ligands that have been simulated shown that their binding affinity was lower than AA5 that reached-44.6753 kcal/mol. Conclusion: This studies conclude that AA5 considerably more potential as a selective inhibitor of iNOS enzyme as an anti-inflammatory.

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