scholarly journals Topological and Reactivity Descriptor of Carisoprodol from DFT and Molecular Docking Approach

2021 ◽  
Vol 26 (1) ◽  
pp. 74-82
Author(s):  
Tarun Chaudhary ◽  
Manoj Kumar Chaudhary ◽  
Bhawani Datt Joshi
Keyword(s):  
Molecular Docking ◽  
Energy Gap ◽  
Topological Analysis ◽  
Docking Simulation ◽  
Vital Role ◽  
Hydrogen Atoms ◽  
Charge Localization ◽  
Donor And Acceptor ◽  
Molecular Stability ◽  
Docking Approach

This study aims to investigate the optimized structure and optimized parameters of carisoprodol from the DFT/B3LYP/6-31G(d,p) level of theory. The molecular electrostatic potential (MEP) map signifies that the positive potential across hydrogen of the amine group (NH2) and the negative potential around the carbonyl groups (C=O). HOMO-LUMO energy gap was found to be 8.1064 eV. The global and local reactivity parameters describe the possible chemical reactive sites in the molecule. The topological analysis of the electron localization function (ELF) and localized orbital locator (LOL) revealed that the charge localization around hydrogen atoms. The hyper-conjugative interaction between donor and acceptor orbital showed that the interaction LP(2) O4→ σ*(O2-C16) plays a vital role in the molecular stability. The molecular docking simulation encircles that the carisoprodol behaves as a good inhibitor with the target protein, Tyrosine-protein kinase ABL.

scholarly journals Potential Mechanism Prediction of Herbal Medicine for Pulmonary Fibrosis Associated with SARS-CoV-2 Infection Based on Network Analysis and Molecular Docking

2021 ◽  
Vol 12 ◽  
Author(s):  
De Jin ◽  
Xuedong An ◽  
Yuqing Zhang ◽  
Shenghui Zhao ◽  
Liyun Duan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Pulmonary Fibrosis ◽  
Signaling Pathways ◽  
Topological Analysis ◽  
Recovery Period ◽  
Treatment Protocol ◽  
Docking Simulation ◽  
Mapk Signaling ◽  
Tnf Α ◽  
Tgf Β1

Background: Coronavirus Disease 2019 (COVID-19) is still a relevant global problem. Although some patients have recovered from COVID-19, the sequalae to the SARS-CoV-2 infection may include pulmonary fibrosis, which may contribute to considerable economic burden and health-care challenges. Convalescent Chinese Prescription (CCP) has been widely used during the COVID-19 recovery period for patients who were at high risk of pulmonary fibrosis and is recommended by the Diagnosis and Treatment Protocol for COVID-19 (Trial Version sixth, seventh). However, its underlying mechanism is still unclear.Methods: In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of CCP, data mining of the disease targets, protein-protein interaction (PPI) network construction, and analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of CCP for pulmonary fibrosis associated with SARS-CoV-2 infection.Results: The active compound of CCP and the candidate targets, including pulmonary fibrosis targets, were obtained through database mining. The Drug-Disease network was constructed. Sixty-five key targets were identified by topological analysis. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the VEGF, Toll-like 4 receptor, MAPK signaling pathway, and TGF-β1 signaling pathways may be involved in pulmonary fibrosis. In the molecular docking analyses, VEGF, TNF-α, IL-6, MMP9 exhibited good binding activity. Findings from our study indicated that CCP could inhibit the expression of VEGF, TNF-α, IL-6, MMP9, TGF-β1 via the VEGF, Toll-like 4 receptor, MAPK, and TGF-β1 signaling pathways.Conclusion: Potential mechanisms involved in CCP treatment for COVID-19 pulmonary fibrosis associated with SARS-CoV-2 infection involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of CCP.

Computational evaluation on molecular stability, reactivity, and drug potential of frovatriptan from DFT and molecular docking approach

2020 ◽  
Vol 1191 ◽  
pp. 113031
Author(s):  
Manoj Kumar Chaudhary ◽  
Anubha Srivastava ◽  
Keshav Kumar Singh ◽  
Poonam Tandon ◽  
Bhawani Datt Joshi
Keyword(s):  
Molecular Docking ◽  
Computational Evaluation ◽  
Molecular Stability ◽  
Docking Approach

scholarly journals Molecular Docking Approach of Natural Compound from Herbal Medicine in Java against Severe Acute Respiratory Syndrome Coronavirus-2 Receptor

2021 ◽  
Vol 9 (A) ◽  
pp. 1181-1186
Author(s):  
Yuyun Yueniwati ◽  
Mokhamad Fahmi Rizki Syaban ◽  
Icha Farihah Deniyati Faratisha ◽  
Khadijah Cahya Yunita ◽  
Dedy Budi Kurniawan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Natural Resources ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Data Bank ◽  
Protein Stabilization ◽  
Hydrogen Atoms ◽  
Cucurbitacin B ◽  
Pubchem Database ◽  
Docking Approach

Indonesia's diversity of natural resources presents an intriguing opportunity for the exploration of potential herbal medicines. Numerous compounds, both purified and crude, have been reported to exhibit antiviral activity. The ACE-2 receptor may be a therapeutic target for SARS-CoV-2 infection. We used a search engine to search for herbal medicines with ACE-2 inhibitory activity to predict the potential inhibition of natural compounds (i.e., theaflavin, deoxypodophyllotoxin, gallocatechin, allicin, quercetin, annonamine, Curcumin, 6-gingerol, and cucurbitacin B) to SARS-CoV2 – ACE-2 complex. We performed molecular docking analysis using the ACE-2 protein target from Protein Data Bank. Protein stabilization was carried out to adjust to the body's physiology, carried out using Pymol by removing water atoms and adding hydrogen atoms. Ligands of active compounds from natural resources were selected and downloaded from the PubChem database, then optimized by Pymol software. The complexes of the tested ligand compounds and ACE-2 receptors, which have a bond strength smaller than the control were selected for analysis.  Theaflavin, Deoxypodophyllotoxin, Gallocatechin, Curcumin, and Cucurbitacin B had a strong bond affinity than the control ligands. Based on our data, deoxypodophylotoxin and Curcumin had the same interaction amino acid residus compare to the control ligand. This study concludes that deoxypodophyllotoxin and Curcumin have the greatest potential to inhibit the formation of the SARS-Cov2-ACE-2 complex; additionally, these compounds exhibit favorable pharmacological and pharmacodynamic properties. It is suggested that additional research be conducted to determine the biological effects of deoxypodopyllotoxin and Curcumin on ACE-2 receptors.

Acetogenins Exhibit Potential BCL-XL Inhibitor for the Induction of Apoptosis in the Molecular Docking Study

2021 ◽  
Vol 18 ◽  
Author(s):  
Noraziah Nordin ◽  
Kaynat Khimani ◽  
Mohd Faiz Abd Ghani
Keyword(s):  
Molecular Docking ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance ◽  
Docking Simulation ◽  
Docking Study ◽  
Biological Properties ◽  
Vital Role ◽  
Molecular Docking Study ◽  
Good Target ◽  
Induction Of Apoptosis

Background: Anti-apoptotic protein BCL-XL plays a vital role in tumorigenesis and cancer chemotherapy resistance, resulting in a good target for cancer treatment. Understanding the function of BCL-XL has driven the progression of a new class of cancer drugs that can mimic its natural inhibitors, BH3-only proteins to trigger apoptosis. This mimicking is initiated through acetogenins due to their excellent biological properties. Acetogenins which can be isolated from Annonaceae plants, have a unique structure along with several oxygenated functionalities. Objective: Based on their biological capability, various acetogenins were studied in the present study and compared alongside with ABT-737 on molecular docking. Methods: The docking simulation of acetogenins was performed using AutoDock Vina software. Results: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than – 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11) and isoannonacin-10-one A (18). Conclusion: These findings indicated that some acetogenins could represent a new potential BCL-XL inhibitor which could mimic the BH3-only protein for the induction of apoptosis in cancer chemotherapy.

scholarly journals Utilizing network pharmacology and molecular docking to explore the underlying mechanism of Guizhi Fuling Wan in treating endometriosis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11087
Author(s):  
Haoxian Wang ◽  
Gang Zhou ◽  
Mingyan Zhuang ◽  
Wei Wang ◽  
Xianyun Fu
Keyword(s):  
Molecular Docking ◽  
Mapk Pathway ◽  
Colorimetric Assay ◽  
Topological Analysis ◽  
Docking Simulation ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Control Group ◽  
Ppi Network ◽  
Active Compounds

Background Guizhi Fuling Wan (GZFLW) is a widely used classical Chinese herbal formulae prescribed for the treatment of endometriosis (EMs). This study aimed to predict the key targets and mechanisms of GZFLW in the treatment of EMs by network pharmacology and molecular docking. Methods Firstly, related compounds and targets of GZFLW were identified through the TCMSP, BATMAN-TCM and CASC database. Then, the EMs target database was built by GeneCards. The overlapping targets between GZFLW and EMs were screened out, and then data of the PPI network was obtained by the STRING Database to analyze the interrelationship of these targets. Furthermore, a topological analysis was performed to screen the hub targets. After that, molecular docking technology was used to confirm the binding degree of the main active compounds and hub targets. Finally, the DAVID database and Metascape database were used for GO and KEGG enrichment analysis. Results A total of 89 GZFLW compounds and 284 targets were collected. One hundred one matching targets were picked out as the correlative targets of GZFLW in treating EMs. Among these, 25 significant hub targets were recognized by the PPI network. Coincidently, molecular docking simulation indicated that the hub targets had a good bonding activity with most active compounds (69.71%). Furthermore, 116 items, including the inflammatory reaction, RNA polymerase, DNA transcription, growth factor activity, and steroid-binding, were selected by GO enrichment analysis. Moreover, the KEGG enrichment analysis results included 100 pathways focused on the AGE-RAGE pathway, HIF pathway, PI3K Akt pathway, MAPK pathway, and TP53 pathway, which exposed the potential mechanisms of GZFLW in treating EMs. Also, the MTT colorimetric assay indicated that the cell proliferation could be inhibited by GZFLW. Compared with the control group, the protein levels of P53, BAX, and caspase3 in the drug groups were all increased in Western blotting results. The results of flow cytometry showed that the percentage of apoptotic cells in the GZFLW group was significantly higher than that in the control group. Conclusion Through the exploration of network pharmacology and molecular docking technology, GZFLW has a therapeutic effect on EMs through multi-target mechanism. This study provided a good foundation for further experimental research.

scholarly journals Prediction of the Active Ingredients, Potential Targets, and Signaling Pathways in ZaoRenDiHuang Capsules for Treatment of Insomnia Based on Network Analysis and Molecular Docking

2020 ◽  
Author(s):  
De Jin ◽  
Jinghua Zhang ◽  
Yuqing Zhang ◽  
Xuedong AN ◽  
Shenghui Zhao ◽  
...  
Keyword(s):  
Data Mining ◽  
Molecular Docking ◽  
Network Analysis ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Topological Analysis ◽  
Docking Simulation ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Active Ingredients

Abstract Background：Insomnia is a major global public health issue with a high incidence, which presents a significant economic burden. Importantly, insomnia is often accompanied by a myriad of symptoms during the daytime, the most common being insomnia dizziness, headache, malaise, fatigue, anxiety, and even contribute to several diseases. However, the action mode of multi-component and multi-target for Chinese medicine could be a promising therapy for insomnia. According to the previous research, the ZaoRenDiHuang (ZRDH) Capsules showed the noteworthy anti-insomnia effect. Up to now, active ingredients, potential targets, and signaling pathways and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential anti-insomnia mechanism of ZRDH.Methods：In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of ZRDH, data mining of the insomnia targets, protein-protein interaction (PPI) network analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of ZRDH for insomnia.Results：In this work, 44 anti-insomnia components of ZRDH and 65 anti-insomnia targets of insomnia were filtrated through database mining. The Drug-Disease network was constructed andfive key components Jujuboside A, Schizandrin A, Schizandrin C, Schizandrin B, and Spinosin, were further obtained. Sixty-five key targets were identified by topological analysis. Sequential studies turned out, NMURl, CAlCR, GABA, TAER2, ORDS, CYS1TR2, HTR1B, TLR4 were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the Neuroactive ligand−receptor interaction, Serotonergic synapse CAMP signaling pathway, HIF−1a signaling pathway, Toll−like receptor signaling pathway, anti-insomnia through data mining and network analysis.Conclusion: In sunmmary, potential mechanisms involved in ZRDH treatment for insomnia involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of ZRDH.

Molecular Docking Approaches to Suggest the Anti-Mycobacterial Targets of Natural Products

2020 ◽  
Author(s):  
Rafael Baptista ◽  
Sumana Bhowmick ◽  
Shen Jianying ◽  
Luis Mur
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Free Energies ◽  
Antibiotic Resistant ◽  
Drug Lead ◽  
Bisbenzylisoquinoline Alkaloids ◽  
Docking Approach ◽  
Global Threat ◽  
Physicochemical And Structural Properties

Tuberculosis (TB) is a major global threat mostly due to the development of antibiotic resistant forms of Mycobacterium tuberculosis, the causal agent of the disease. Driven by the pressing need for new anti-mycobacterial agents, several natural products (NPs) have been shown to have in vitro activities against M. tuberculosis. The utility of any NP as a drug lead is augmented when the anti-mycobacterial target(s) is unknown. To suggest these, we used a molecular docking approach to predict the interactions of 53 selected anti-mycobacterial NPs against known ‘druggable’ mycobacterial targets ClpP1P2, DprE1, InhA, KasA, PanK, PknB and Pks13. The docking scores / binding free energies were predicted and calculated using AutoDock Vina along with physicochemical and structural properties of the NPs, using PaDEL descriptors. These were compared to the established inhibitor (control) drugs for each mycobacterial target. The specific interactions of the bisbenzylisoquinoline alkaloids 2-nortiliacorinine, tiliacorine and 13’-bromotiliacorinine against the targets PknB and DprE1 (-11.4, -10.9 and -9.8 kcal.mol-1 ; -12.7, -10.9 and -10.3 kcal.mol-1 , respectively) and the lignan αcubebin and Pks13 (-11.0 kcal.mol-1 ) had significantly superior docking scores compared to controls. Our approach can be used to suggest predicted targets for the NP to be validated experimentally but these in silico steps are likely to facilitate drug optimisation.

Investigation of Adsorption Effect of Carbon Monoxide on Coniine: A DFT Study

2021 ◽  
Vol 17 ◽  
Author(s):  
Siyamak Shahab ◽  
Masoome Sheikhi ◽  
Mehrnoosh Khaleghian ◽  
Marina Murashko ◽  
Mahin Ahmadianarog ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Gas Phase ◽  
Density Functional ◽  
Energy Gap ◽  
Adsorption Effect ◽  
Chemical Shift Tensors ◽  
Solvent Water ◽  
Donor And Acceptor ◽  
Before And After ◽  
Electron Donor And Acceptor

: For the first time in the present study, the non-bonded interaction of the Coniine (C8H17N) with carbon monoxide (CO) was investigated by density functional theory (DFT/M062X/6-311+G*) in the gas phase and solvent water. The adsorption of the CO over C8H17N was affected on the electronic properties such as EHOMO, ELUMO, the energy gap between LUMO and HOMO, global hardness. Furthermore, chemical shift tensors and natural charge of the C8H17N and complex C8H17N/CO were determined and discussed. According to the natural bond orbital (NBO) results, the molecule C8H17N and CO play as both electron donor and acceptor at the complex C8H17N/CO in the gas phase and solvent water. On the other hand, the charge transfer is occurred between the bonding, antibonding or nonbonding orbitals in two molecules C8H17N and CO. We have also investigated the charge distribution for the complex C8H17N/CO by molecular electrostatic potential (MEP) calculations using the M062X/6-311+G* level of theory. The electronic spectra of the C8H17N and complex C8H17N/CO were calculated by time dependent DFT (TD-DFT) for investigation of the maximum wavelength value of the C8H17N before and after the non-bonded interaction with the CO in the gas phase and solvent water. Therefore, C8H17N can be used as strong absorbers for air purification and reduce environmental pollution.

Quantitative structure-activity relationship model, molecular docking simulation and computational design of some novel compounds against DNA gyrase receptor.

2020 ◽  
Vol 16 ◽  
Author(s):  
Shola Elijah Adeniji
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Binding Energy ◽  
Biological Activities ◽  
Docking Simulation ◽  
Dna Gyrase ◽  
Computational Design ◽  
Multi Drug Resistance ◽  
Drug Candidate ◽  
Standard Drug

Introduction: Mycobacterium tuberculosis has instigated a serious challenge toward the effective treatment of tuberculosis. The reoccurrence of the resistant strains of the disease to accessible drugs/medications has mandate for the development of more effective anti-tubercular agents with efficient activities. Time expended and costs in discovering and synthesizing new hypothetical drugs with improved biological activity have been a major challenge toward the treatment of multi-drug resistance strain M. tuberculosis (TB). Meanwhile, to solve the problem stated, a new approach i.e. QSAR which establish connection between novel drugs with a better biological against M. tuberculosis is adopted. Methods: The anti-tubercular model established in this study to forecast the biological activities of some anti-tubercular compounds selected and to design new hypothetical drugs is subjective to the molecular descriptors; MATS7s, SM1_DzZ, SpMin4_Bhv, TDB3v and RDF70v. Ligand-receptor interactions between quinoline derivatives and the receptor (DNA gyrase) was carried out using molecular docking technique by employing the PyRx virtual screening software and discovery studio visualizer software. Furthermore, docking study indicates that compounds 20 of the derivatives with promising biological activity have the utmost binding energy of -17.79 kcal/mol. Results: Meanwhile, the interaction of the standard drug; isoniazid with the target enzyme was observed with the binding energy -14.6 kcal/mol which was significantly lesser than the binding energy of the ligand (compound 20).Therefore, compound 20 served as a template structure to designed compounds with more efficient activities. Among the compounds designed; compounds 20p was observed with better anti-tubercular activities with more prominent binding affinities of -24.3kcal/mol. Conclusion: The presumption of this research aid the medicinal chemists and pharmacist to design and synthesis a novel drug candidate against the tuberculosis. Moreover, in-vitro and in-vivo test could be carried out to validate the computational results.

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