scholarly journals Docking studies in targeting proteins involved in cardiovascular disorders using phytocompounds from Terminalia arjuna

2020 ◽  
Author(s):  
Vikas Kumar ◽  
Nitin Sharma ◽  
Anuradha Sourirajan ◽  
Prem Kumar Khosla ◽  
Kamal Dev
Keyword(s):  
Molecular Docking ◽  
3D Structure ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Studies ◽  
Terminalia Arjuna ◽  
Structure Based Drug Design ◽  
Lipinski’S Rule ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractTerminalia arjuna (Roxb.) Wight and Arnot (T. arjuna) commonly known as Arjuna has been known for its cardiotonic nature in heart failure, ischemic, cardiomyopathy, atherosclerosis, myocardium necrosis and also has been used in the treatment of different human disorders such as blood diseases, anaemia and viral diseases. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant cardioprotective activity. Since Protein-Ligand interactions play a key role in structure-based drug design, therefore with the help of molecular docking, we screened 19 phytochemicals present in T. arjuna and investigated their binding affinity against different cardiovascular target proteins. The three-dimensional (3D) structure of target cardiovascular proteins were retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 19 phytochemicals using Autodock vina. Molecular docking and drug-likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their cardio protective activity. Among all selected phytocompounds, arjunic acid, arjungenin, and terminic acid were found to fulfill all ADMET rules, drug likeness, and are less toxic in nature. Our studies, therefore revealed that these three phytochemicals from T. arjuna can be used as promising candidates for developing broad spectrum drugs against cardiovascular diseases.

scholarly journals Mechanistic Validation of an Ergogenic T. arjuna Standardized Extract (Oxyjun®) Using a Molecular Docking Approach

2021 ◽  
pp. 54-63
Author(s):  
Kavita Pandey ◽  
Gursimran Kaur Uppal ◽  
Ratna Upadhyay
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Terminalia Arjuna ◽  
Lipinski’S Rule ◽  
Protein Ligand Interactions ◽  
Potential Efficacy ◽  
Ligand Interactions ◽  
Docking Approach ◽  
Cardio Vascular ◽  
Botanical Extract

The bark of the tree Terminalia arjuna commonly referred as Arjuna is widely used in Ayurveda as a therapeutic agent for heart disease. More recently, a proprietary botanical extract of T. arjuna with tradename, Oxyjun®, demonstrated cardiotonic and ergogenic benefits for the first time in a younger and healthier population. However, the mechanism of action and biological actives of this novel sports ingredient were not clear. A molecular docking approach was adopted to understand the protein-ligand interactions and establish the most probable mechanism(s) of cardio vascular actions of the phytoconstituents of the T. arjuna standardized extract (TASE). Twenty-one phytochemicals (ligands) were chosen from Arjuna and their binding affinities against eight proteins serving cardiovascular functions (target proteins) were investigated. Autodock Vina was used to carry out the molecular docking studies. Potential efficacy in humans was assessed on the basis of ADMET properties and Lipinski’s Rule of 5. We found that arjunic acid, arjungenin, arjunetin, arjunglucoside1, chrysin, kaempferol, luteolin, rhamnetin and taxifolin demonstrated good docking scores and bioactivity.

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.

scholarly journals SOLATION, CHARACTERIZATION, AND DOCKING STUDIES OF ISOLATED COMPOUNDS AS ANTIDIABETIC MOLECULES FROM CRESSA CRETICA

2020 ◽  
pp. 84-91
Author(s):  
SANGEETA RANI ◽  
KAVITA GAHLOT ◽  
ARVIND KUMAR
Keyword(s):  
Molecular Docking ◽  
Spectroscopic Analysis ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Lead Target ◽  
Coarse Powder ◽  
Autodock 4.0

Objective: The purpose of this study was to investigate the diabetic effect of phytocompounds isolated from Cressa cretica Linn. using spectroscopic analysis and molecular docking studies. Methods: Coarse powder of the whole plant of C. cretica was extracted with methanol, extracted part was subjected to silica column isolation, and two compounds: 2-Isopropyl-4-(1-methyl-dodeca-2,4-dienyloxy)-benzene-1,3,5-triol (Compound CN-01) and 11-Methyl-dodeca-2,4,6,8,10-pentenoic acid 2,3-dihydroxy-5-methyl-phenyl ester (Compound CN-02) were isolated in pure form. The three-dimensional structure of target protein was downloaded from PDB (www.rcsb.org) Protein Data Bank, Ligand file CN – 01 and CN – 02 were converted to MDL Molfile (V2000) format using ChemSketch 2017.2.1. These files could not be used directly in AutoDock 4.0 tools; thus, they were first converted to PDB files using an open babel tool. Results: Compounds were revealed through spectroscopic analysis and screened using AutoDock 4.0 tools. Docking study recommended that CN – 01 and CN – 02 an existing phytochemical from the plant of C. cretica had the highest fitness docking score and hence could be a potent antidiabetic drug. Conclusion: In this investigation, we docked the receptor (glycogen phosphorylase protein) holds a promising lead target formation against diabetes based on molecular docking analysis (minimum hydrogen bond length and maximum docked score). Thus, these compounds can be effectively used as drugs for treating diabetes which is predicted on the basis of docking scores.

scholarly journals The structural diversity of ginsenosides affects their cholinesterase inhibitory potential

2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Eda Özturan Özer ◽  
Oya Unsal Tan ◽  
Suna Turkoglu
Keyword(s):  
Molecular Docking ◽  
Enzyme Inhibitor ◽  
Direct Interaction ◽  
Structural Diversity ◽  
Docking Studies ◽  
Catalytic Triad ◽  
Active Components ◽  
Molecular Docking Studies ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractBackground/ObjectiveGinsenosides, the major active components of the ginseng, are known to have various effects on nervous systems. The present study aimed to clarify the inhibition potentials of ginsenosides Rb1, Rc, Re and Rg1 on acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activities, and to evaluate the underlying mechanisms of inhibitions provided by protein-ligand interactions considering their probable candidates of prodrug.Materials and methodsThe inhibitory mechanisms of ginsenosides related with their structural diversity were analyzed kinetically and protein-ligand interactions for both enzymes were evaluated with most potent ginsenosides, by molecular docking studies.ResultsGinsenosides Re and Rg1, with sugar moieties attached to the C-6 and C-20 positions of core structure were found to possess the most powerful inhibitory effect on AChE and BChE activities. Molecular docking studies have been confirmed by kinetic studies. Ginsenosides having a direct interaction with amino acid residues belonging to the catalytic triad revealed the most powerful inhibition with lowest enzyme-inhibitor dissociation constant (Ki) values.ConclusionsGinsenosides Re and Rg1, either alone or in a specific combination, may provide beneficial effects on neurodegenerative pathologies in therapeutic terms.

scholarly journals MOLECULAR DOCKING STUDIES FOR THE COMPARATIVE ANALYSIS OF DIFFERENT BIOMOLECULES TO TARGET HYPOXIA INDUCIBLE FACTOR-1α

2017 ◽  
Vol 9 (4) ◽  
pp. 83 ◽  
Author(s):  
Niraj Kumar Jha ◽  
Pravir Kumar
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Hypoxia Inducible Factor ◽  
3D Structure ◽  
Amyloid Β ◽  
Docking Studies ◽  
Therapeutic Window ◽  
Hypoxic Exposure ◽  
Amyloid Β Protein ◽  
Lipinski’S Rule

Objective: Hypoxia plays a significant role in governing many vital signalling molecules in the central nervous system (CNS). Hypoxic exposure has also been depicted as a stimulus for oxidative stress, increase in lipid peroxidation, DNA damage, blood-brain dysfunction, impaired calcium (Ca2+) homoeostasis and agglomeration of oxidized biomolecules in neurons, which act as a novel signature in diverse neurodegenerative and oncogenic processes. On the contrary, the presence of abnormally impaired expression of HIF-1α under hypoxic insult could serve as an indication of the existence of tumors and neuronal dysfunction as well. For instance, under hypoxic stress, amyloid-β protein precursor (AβPP) cleavage is triggered due to the higher expression of HIF-1α and thus leads to synaptic loss. The objective of this research is to perform comparative studies of biomolecules in regulating HIF-1α activity based on in silico approaches that could establish a potential therapeutic window for the treatment of different abnormalities associated with impaired HIF-1α.Methods: We employed various in silico methods such as drug-likeness parameters namely Lipinski filter analysis, Muscle tool, SWISS-MODEL, active site prediction, Auto Dock 4.2.1 and LigPlot1.4.5for molecular docking studies.Results: 3D structure of HIF-1α was generated and Ramachandran plot obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favoured regions. 0% residues in additionally allowed and 0.5% disallowed regions of the HIF-1α protein. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. Cast P server used to predict the ligand binding site suggests that this protein can be utilised as a potential drug target. Finally, we have found Naringenin to be most effective amongst three biomolecules in modulating HIF-1α based on minimum inhibition constant, Ki and highest negative free energy of binding with the maximum interacting surface area during docking studies.Conclusion: The present study outlines the novel potential of Biomolecules in regulating HIF-1α activity for the treatment of different abnormalities associated with impaired HIF-1α.

Identification of Novel Human Serum Albumin (SA) Inhibitors from Scoparia Dulsis for Urolithiasis

2020 ◽  
Vol 16 (3) ◽  
pp. 308-317 ◽  
Author(s):  
Divya Shaji
Keyword(s):  
Binding Energy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
3D Structure ◽  
Data Bank ◽  
Major Drawback ◽  
Structure Based Drug Design ◽  
Lipinski’S Rule ◽  
Extracorporeal Shock Wave

Background:: Urolithiasis is the process of forming stones in the kidney, bladder, and/or urinary tract. It has been reported that kidney stones are the third most common disorder among urinary diseases. At present, surgical procedures and Extracorporeal Shock Wave Lithotripsy (ESWL) are commonly employed for the treatment of Urolithiasis. The major drawback of these procedures is the recurrence of stones. Methods: This study aimed to identify potential natural inhibitors against human Serum Albumin (SA) from the plant Scoparia Dulsis for Urolithiasis. As protein-ligand interactions play a key role in structure- based drug design, this study screened 26 compounds from Scoparia Dulsis and investigated their binding affinity against SA by using molecular docking. The three dimensional (3D) structure of SA was retrieved from Protein Data Bank (PDB) and docked with PubChem structures of 26 compounds using PyRX docking tool through Autodock Vina. Moreover, a 3D similarity search on the PubChem database was performed to find the analogs of best scored compound and docking studies were performed. Drug-likeness studies were made using Swiss ADME and Lipinski’s rule of five was performed for the compounds to evaluate their anti-urolithiatic activity. Results: The results showed that citrusin c (Eugenyl beta-D-glucopyranoside) exhibited best binding energy of -8.1 kcal/mol with SA followed by aphidicolin, apigenin, luteolin and scutellarein. Two compounds (PubChem CID 46186820, PubChem CID 21579141) analogous to citrusin c were selected based on the lowest binding energy. Conclusion: This study, therefore, reveals that these compounds could be promising candidates for further evaluation for Urolithiasis prevention or management.

scholarly journals Structure Based Design and Molecular Docking Studies for Phosphorylated Tau Inhibitors in Alzheimer’s Disease

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 260 ◽  
Author(s):  
Jangampalli Pradeepkiran ◽  
P. Reddy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Toxicity Tests ◽  
Phosphorylated Tau ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Alternative Drug

The purpose of our study is to identify phosphorylated tau (p-tau) inhibitors. P-tau has recently received great interest as a potential drug target in Alzheimer’s disease (AD). The continuous failure of Aβ-targeted therapeutics recommends an alternative drug target to treat AD. There is increasing evidence and growing awareness of tau, which plays a central role in AD pathophysiology, including tangles formation, abnormal activation of phosphatases/kinases, leading p-tau aggregation in AD neurons. In the present study, we performed computational pharmacophore models, molecular docking, and simulation studies for p-tau in order to identify hyperphosphorylated sites. We found multiple serine sites that altered the R1/R2 repeats flanking sequences in the tau protein, affecting the microtubule binding ability of tau. The ligand molecules exhibited the p-O ester scaffolds with inhibitory and/or blocking actions against serine residues of p-tau. Our molecular docking results revealed five ligands that showed high docking scores and optimal protein-ligand interactions of p-tau. These five ligands showed the best pharmacokinetic and physicochemical properties, including good absorption, distribution, metabolism, and excretion (ADME) and admetSAR toxicity tests. The p-tau pharmacophore based drug discovery models provide the comprehensive and rapid drug interventions in AD, and tauopathies are expected to be the prospective future therapeutic approach in AD.

scholarly journals Ligand docking and binding site analysis with pymol and autodock/vina

2015 ◽  
Vol 4 (2) ◽  
pp. 168 ◽  
Author(s):  
Mohd. Ahmar Rauf ◽  
Swaleha Zubair ◽  
Asim Azhar
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Three Dimensional ◽  
Structural Features ◽  
Docking Studies ◽  
Ligand Docking ◽  
Structure Based Drug Design ◽  
Site Analysis ◽  
User Friendly ◽  
Autodock 4.2

<p>Docking of various therapeutically important chemical entities to the specific target sites offers a meaningful strategy that may have tremendous scope in a drug design process. For a thorough understanding of the structural features that determine the strength of bonding between a ligand with its receptor, an insight to visualize binding geometries and interaction is mandatory. Bioinformatical as well as graphical software ‘PyMOL’ in combination with the molecular docking suites Autodock and Vina allows the study of molecular combination to visualize and understand the structure-based drug design efforts. In the present study, we outlined a user friendly method to perform molecular docking using vina and finally the results were analyzed in pymol in both two as well as three-dimensional orientation. The operation bypasses the steps that are involved in docking using cygwin terminal like formation of gpf and dpf files. The simple and straight-forward operation method does not require formal bioinformatics training to apprehend molecular docking studies using AutoDock 4.2 program.</p>

scholarly journals In silico screening of drug inhibitors of SARS-CoV-2RNA-dependent RNA polymerase target

2021 ◽  
Vol 63 (4) ◽  
pp. 47-54
Author(s):  
Thanh Tung Bui ◽  
◽  
Bao Kim Nguyen ◽  
Minh Ngoc Le ◽  
The Toan Nguyen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
In Silico ◽  
Profile Analysis ◽  
3D Structure ◽  
Data Bank ◽  
Health Concern ◽  
Pharmacokinetic Parameters ◽  
Rna Dependent Rna Polymerase ◽  
Lipinski’S Rule

Objectives: the COVID-19 pandemic triggering acute respiratory syndrome has become a major global health concern. After one year into this pandemic, special therapies for COVID-19 remain an unprecedented challenge to mankind and finding drugs to treat this disease is extremely urgent. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) enzyme that regulates viral replication has been examined as a potential therapeutic target for the inhibition of SARS-CoV-2 infection. In this study, the authors evaluated the ability of RNA-dependent RNA polymerase drug inhibitors by using an in silico molecular docking model. Methods: the 3D structure of RdRp enzyme (PDB ID:6M71, resolution of 2.90 Å) was derived from the Protein Data Bank RCSB. The ligand structures were collected from DrugBank for the RdRp target. Molecular docking was done by AutoDock Vina software. Lipinski’s rule of five is used to compare compounds with drug-like and non-drug-like properties. Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. Results: based on the DrugBank database, we collected 192 antiviral molecules and compared them to remdesivir, which has inhibitory activity with this protein target. Results showed that 26 out of 192 compounds have a higher ability to inhibit the SARS-CoV-2 RdRp enzyme than remdesivir. Next, 6 drugs were selected by visually inspecting the docking results with focus on the main interaction between crucial residues at the binding site of the SARS-CoV-2 RdRp enzyme. For the visual inspection, the existence of polar interactions with ASP760 and ASP761 were utilised as the preference criterion. Finally, Lipinski’s rule of 5 criteria and absorption, distribution, metabolism, excretion and toxicity (ADMET) profile analysis suggested five drugs that have good pharmacokinetic properties. Conclusions: these drugs were dihydroergotamine, sofosbuvir, nilotinib, tipranavir, and darunavir and may be used as anti-SARS-CoV-2 agents.

scholarly journals MOLECULAR DOCKING STUDIES OF ISOLATED FLAVONOIDS COMPOUNDS FROM AMARANTHUS TRISTIS LINN. AS ALPHA-AMYLASE AND ALPHA-GLUCOSIDASE ACTIVATORS

2018 ◽  
Vol 11 ◽  
Author(s):  
Sundar Rajan T ◽  
Vijey Aanandhi M
Keyword(s):  
Molecular Docking ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Studies ◽  
Alpha Amylase ◽  
Dimensional Structure ◽  
Novel Targets ◽  
Alpha Glucosidase ◽  
Protein Data Bank Database

Aim: Aim of this work on in silico approach to used to access the use of flavonids compounds of nutritionally enriched plant Amaranthus tristis Linn.Methods: Bioflavonoids of rutin isolated from A. tristis Linn. and active agents receptor such as alpha-amylase (1SMD) and alpha-glucosidase (3wy1) activators. Three-dimensional structure of receptors was obtained from protein data bank database and biocomponents such as isoflavones and flavonones of A. tristis were downloaded from database like USDA. Docking studies of insulin receptor with A. tristis biocomponents for isoflavones and flavonones were performed using AutoDock - 1.5.6 software.Results: Compounds from A. tristis Linn. showed better binding features with the alpha-amylase and alpha-glycosidase. Thus, these compounds can be effectively used as drugs for treating diabetes which is predicted on the basis of docking scores.Conclusion: The insights gained in this work can be further used in experimental studies for designing antidiabetic drugs with novel targets and mode of action.

Sign in / Sign up

Export Citation Format

Share Document