scholarly journals In silico approach of receptor-ligand binding and interaction: Established phytoligands from Tagetes errecta Linn. against bacterial β-glucosidase receptor

2019 ◽  
Vol 9 (1-s) ◽  
pp. 125-131
Author(s):  
Madhumita Lahiri ◽  
Partha Talukdar ◽  
Soumendra Nath Talapatra
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Ligand Binding ◽  
Antimicrobial Agents ◽  
Volatile Oil ◽  
Competitive Inhibitor ◽  
Ornamental Plant ◽  
Binding Interaction ◽  
Receptor Ligand ◽  
Energy Value

The medicinal plant, Tagetes errecta Linn. is a common ornamental plant and leaves of this plant are containing phytochemicals (volatile oil) that inhibit the growth of bacteria, fungi and known natural antimicrobial agents. The objective of the present study was to detect receptor-ligand binding energy and interaction through molecular docking for phytoligands established in the leaves of T. errecta against β-glucosidase receptor (PDB ID: 3AHZ). Molecular docking was performed by using PyRx (Version 0.8) for the structure-based virtual screening and visualized the interaction in the molecular graphic laboratory (MGL) tool (Version 1.5.6). Among 25 phytochemicals and 2 synthetic compounds (Carbendazim and 2-Amino-2-hydroxymethyl-propane-1,3-diol), binding energy value was obtained highest in Bicyclogermacrene (-6.4 Kcal/mol) and lowest in Octanol (-4.4 Kcal/mol) and Carbendazim and 2-Amino-2-hydroxymethyl-propane-1,3-diol showed -6.7 Kcal/mol and -3.5 Kcal/mol all of these showed no hydrogen bonding. The binding interaction of target protein with this phytocompound found binding at the mouth of the active site may be treated as competitive inhibitor. In conclusion, phytocompound Bicyclogermacrene can be alternative of synthetic fungicide as per binding energy value and interaction. It is suggesting further pharmacological and toxicological assay with this phytocompound after isolation from ornamental plant (T. errecta).

scholarly journals Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1051
Author(s):  
Edgardo Becerra ◽  
Giovanny Aguilera-Durán ◽  
Laura Berumen ◽  
Antonio Romo-Mancillas ◽  
Guadalupe García-Alcocer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Binding Sites ◽  
Adenosine Monophosphate ◽  
Competitive Inhibitor ◽  
Umbrella Sampling ◽  
Coarse Grained ◽  
Nucleotide Polymorphisms

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.

scholarly journals Molecular docking-based test for affinities of two ligands toward vasopressin and oxytocin receptors.

2001 ◽  
Vol 48 (1) ◽  
pp. 131-135 ◽  
Author(s):  
R Slusarz ◽  
R Kaźmierkiewicz ◽  
A Giełdoń ◽  
B Lammek ◽  
J Ciarkowski
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Ligand Binding ◽  
Effective Procedure ◽  
Amino Acid Residues ◽  
Receptor Ligand ◽  
Docking Simulations ◽  
Oxytocin Receptors ◽  
Developing Area

Molecular docking simulations are now fast developing area of research. In this work we describe an effective procedure of preparation of the receptor-ligand complexes. The amino-acid residues involved in ligand binding were identified and described.

scholarly journals New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 178 ◽  
Author(s):  
Mahadev Patil ◽  
Anurag Noonikara-Poyil ◽  
Shrinivas D. Joshi ◽  
Shivaputra A. Patil ◽  
Siddappa A. Patil ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Growth Inhibition ◽  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Bacterial Strains ◽  
Binding Interaction ◽  
Urea Derivatives ◽  
Molecular Docking Studies

A series of new urea derivatives, containing aryl moieties as potential antimicrobial agents, were designed, synthesized, and characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. All newly synthesized compounds were screened in vitro against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). Variable levels of interaction were observed for these urea derivatives. However, and of major importance, many of these molecules exhibited promising growth inhibition against Acinetobacter baumannii. In particular, to our delight, the adamantyl urea adduct 3l demonstrated outstanding growth inhibition (94.5%) towards Acinetobacter baumannii. In light of this discovery, molecular docking studies were performed in order to elucidate the binding interaction mechanisms of the most active compounds, as reported herein.

Synthesis of novel NSAIDs linked to triazolyl-oxadiazole heterocyclic compounds as more comprehensive antimicrobial agents: A computational molecular docking

2021 ◽  
Vol 17 ◽  
Author(s):  
Shaik Adamshafi ◽  
Venkatarao Veera ◽  
Mohan Rao SVM ◽  
Kishore Pilli VVN
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Active Site ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Solubility Parameters ◽  
Diffusion Method ◽  
Binding Interaction ◽  
Protein Database ◽  
Chemical Structures

Introduction: Progress in the development of triazolyl-oxadiazoles is a bisphosphonate-700 inhibitor is still continuing with an outcome of the good scaffold as oxadiazole as well as triazoles individually for antibacterial activity. Hence, we proposed a suitable approach for the synthesis of dual heterocyclic analogues consisting of the therapeutically used non steroidal anti-inflammatory drugs in a combined form and evaluated for their antibacterial, antifungal activities, docking studies. Methods: The chemical structures were confirmed by various spectroscopic methods like IR, 1H NMR, 13C NMR, mass, and elemental analysis. The antibacterial, antifungal activity of these compounds was screened against Gram-positive, Gram-negative bacteria and fungal stains by agar well diffusion method. The crystal structure of S. aureus complexed with active site of bisphosphonate BPH-700 (2ZCS) was obtained from the Protein Database (PDB, http://www.rcsb.org). Molecular properties, drug likeness score, lipophilicity and solubility parameters by Molinspiration and Molsoft software. 7f (2-NO2, 5-Ome), 7g (3-Cl, 4-Cl), 7a (2-NO2) Results: Among the synthesised NSAID-triazolyl-oxadiazole containing 2-nitro-5-methoxy (7f), 3,4-dichloro (7g) derivatives were found to be high active antibacterial agents against S. aureus, E. coli with MICs 16, 19 μg/mL respectively. 2-nitro-5-methoxy (7f), 4-bromo (7h) and 2-nitro (7a) derivatives displayed superior antifungal activity against A. niger and MICs 56, 76, 130 μg/mL respectively. From molecular docking NSAID linked to 3,4-dichloro analogue (7g) revealed stronger binding interaction (ΔG =7.90 Kcal/Mol) with amino acids Asp49 (1.19 A˚), Arg45 (2.17 A˚), Lys17, Lys46 in the active site of S. aureus complexed with bisphosphonate Bph-700 (2ZCS). The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial screening as oral bioavailable drugs/leads. Maximum drug likeness model score 0.49, 0.41 was found for compounds 7h, 7b. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms. The compounds showed suitable drug like properties and are expected to present good bioavailability profile. Discussion: An efficient combination of molecular modeling and biological activity provided an insight into QSAR guide lines that could aid in further development of these derivatives.

scholarly journals Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine

2020 ◽  
Author(s):  
Roopa Guthappa
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Sites ◽  
Antiviral Drug ◽  
Docking Studies ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Acetyl Cysteine

<p><b>To</b></p> <p><b>Respected Sir/Madam</b> </p> <p>Chemarxiv</p> <p> </p> <p><b>Respected Sir/Madam</b> </p> <p> </p> <p><b>Sub</b>: submission of preprint of article to Chemarxiv for online publication.</p> <p> </p> <p>I am herewith submitting the preprint of an article entitled “Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS Cov 2 protease and its comparison with hydroxychloroquine” for possible publication in “Chemarxiv”.</p> <p> </p> <p>In this article, we have evaluated the binding abilities of N-acetyl cysteine, zinc acetyl cysteine and niclosamide (antiviral drug) with SARS-COV-2 protease. All the four compounds investigated are effective and selectively bind to active sites of main protease. N-acetyl cysteine being a derivative of cysteine interacts with Cys-145, His-163, Gly-143 of COV-2 protease, zinc acetyl cysteine binds to Gly-143, Ser-144, Cys-145, Glu-166 of COV-2 protease and niclosamide bind to Glu-166, Cys-145, His 41 of main protease. The data has been compared with hydroxychloroquine which effectively binds to Cys-145, Glu-166, Arg-188. The binding affinities of N-acetyl cysteine, zinc-acetyl cysteine and niclosamide are -4.24, -4.29 and -7.5 kcal mol<sup>-1</sup> while for hydroxychloroquine it is -6.66 kcal mol<sup>-1</sup>. Niclosamide with its lowest binding energy interacts with His-41 and Cys-145 which may be the first molecule to show such binding interaction. The results indicate that N-acetyl cysteine, zinc-acetyl cysteine and niclosamide can also be explored for the treatment for SARS COV-2 as an alternative for hydroxychloroquine.</p> <p>I hope that the manuscript will full fill the journal’s requirements and will get accepted for publication. </p> <p>Thanking you</p> <p> </p> <p>With regards</p> <p>Roopa Guthappa</p> <p><a href="mailto:[email protected]">[email protected]</a></p>

scholarly journals Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine

2020 ◽  
Author(s):  
Roopa Guthappa
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Sites ◽  
Antiviral Drug ◽  
Docking Studies ◽  
Binding Affinities ◽  
Binding Interaction ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Acetyl Cysteine

<p><b>To</b></p> <p><b>Respected Sir/Madam</b> </p> <p>Chemarxiv</p> <p> </p> <p><b>Respected Sir/Madam</b> </p> <p> </p> <p><b>Sub</b>: submission of preprint of article to Chemarxiv for online publication.</p> <p> </p> <p>I am herewith submitting the preprint of an article entitled “Molecular docking studies of N-acetyl cysteine, zinc acetyl cysteine and niclosamide on SARS Cov 2 protease and its comparison with hydroxychloroquine” for possible publication in “Chemarxiv”.</p> <p> </p> <p>In this article, we have evaluated the binding abilities of N-acetyl cysteine, zinc acetyl cysteine and niclosamide (antiviral drug) with SARS-COV-2 protease. All the four compounds investigated are effective and selectively bind to active sites of main protease. N-acetyl cysteine being a derivative of cysteine interacts with Cys-145, His-163, Gly-143 of COV-2 protease, zinc acetyl cysteine binds to Gly-143, Ser-144, Cys-145, Glu-166 of COV-2 protease and niclosamide bind to Glu-166, Cys-145, His 41 of main protease. The data has been compared with hydroxychloroquine which effectively binds to Cys-145, Glu-166, Arg-188. The binding affinities of N-acetyl cysteine, zinc-acetyl cysteine and niclosamide are -4.24, -4.29 and -7.5 kcal mol<sup>-1</sup> while for hydroxychloroquine it is -6.66 kcal mol<sup>-1</sup>. Niclosamide with its lowest binding energy interacts with His-41 and Cys-145 which may be the first molecule to show such binding interaction. The results indicate that N-acetyl cysteine, zinc-acetyl cysteine and niclosamide can also be explored for the treatment for SARS COV-2 as an alternative for hydroxychloroquine.</p> <p>I hope that the manuscript will full fill the journal’s requirements and will get accepted for publication. </p> <p>Thanking you</p> <p> </p> <p>With regards</p> <p>Roopa Guthappa</p> <p><a href="mailto:[email protected]">[email protected]</a></p>

scholarly journals Molecular Docking, Design and Pharmacokinetics Study of Some Anti-Epilepsy Compounds

2021 ◽  
Vol 15 (5) ◽  
pp. 67
Author(s):  
Gideon Adamu Shallangwa ◽  
Adamu Uzairu ◽  
Usman Abdulfatai
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Simulation Software ◽  
The Body ◽  
Drug Candidate ◽  
Binding Interaction ◽  
Docking Simulations ◽  
Pharmacokinetic Properties ◽  
In Silico Molecular Docking

To complement experimental study, in-silico molecular docking was carried out to access and understand the interacting binding energy dynamism of some experimental potent anti-epilepsy compounds on the GABAT enzyme&rsquo;s (A causative agent for epilepsy disorder) binding site. The Autoduck vina docking option of Pyrx multipurpose simulation software was used in this study to perform docking simulations. Four anti-epilepsy drug (AED) candidates was designed (Anti-epilepsy disorders) through a structural based drug technique. All the designed AED candidates shows stable binding interaction energies. Out of the four designed compounds, 9-decyl-8-methyl-6-(1H-1, 2, 4-triazol-1-yl)-9H-purine shows better binding energy with GABAT. The docked energy score of the compound (7.8Kcal/mole) was better than the binding energy scores of the standard anti-epilepsy compounds, Carbamazepine (-6.5kcal/mole) and Valproate (-4.5kcal/mole). With this level of interaction, this drug candidate could bind better on the enzyme&rsquo;s binding site. Also, the pharmacokinetic properties investigation revealed that all designed AED candidates could be synthesized easily, absorbed, distributed, metabolized and excreted from the body. Therefore, this drug candidate could be synthesized and used effectively for the treatment and management of epilepsy disorder.

scholarly journals Antagonistic Mechanism of Chalcone Derivatives Against Human Estrogen Alpha of Breast Cancer Using Molecular Dynamic Simulation

2018 ◽  
Vol 34 (6) ◽  
pp. 2735-2741
Author(s):  
Muchtaridi Muchtaridi ◽  
Muhammmad Jajuli ◽  
Muhammad Yusuf
Keyword(s):  
Breast Cancer ◽  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Computational Simulation ◽  
Docking Simulation ◽  
Breast Adenocarcinoma ◽  
Binding Interaction ◽  
A Value ◽  
Poisson Boltzmann

2’,4’-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) that isolated from Eugenia aquea Burm f. leaves has a potential anticancer activity against human breast adenocarcinoma cell lines (MCF-7). The objective of this study was to modify ChalcEA to increase its activity as an antagonist of breast cancer with computational simulation approach. A molecular docking simulation was done against the modification structure of ChalcEA with Autodock4 to determine binding interaction between ChalcEA and hERα receptor agonists (PDB ID 1g50). Subsequently, the structure with the smallest bond energy value from the docking result was simulated using molecular dynamics to see its stability within a certain time. The results of molecular docking showed that ChalcEA modification which has a phenol group and pyrazole (MK2) had the free binding energy (ΔG) with a value of -10.2 kcal/mol and bonding hydrogen with GLU353 and ARG394, while estradiol had a value of ΔG=-10.7 kcal/mol. Based on molecular dynamics results, the determination of binding energy was gained using MMPBSA (Molecular Mechanics Poisson-Boltzmann and Surface Area) calculation methods. The MK2 has the better affinity than estradiol with a value of ΔGTotal=-45.10 kcal/mol, while estradiol was amounted to -40.86 kcal /mol. This study suggests that the MK2 might be potential as an antagonist to the hERα of breast cancer.

scholarly journals Effects Of Herbicides And Fungicides On The Soil Chitinolytic Activity. A Molecular Docking Approach

2015 ◽  
Vol 22 (3) ◽  
pp. 439-450
Author(s):  
Diana Larisa Vlădoiu ◽  
Marioara Nicoleta Filimon ◽  
Vasile Ostafe ◽  
Adriana Isvoran
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Active Sites ◽  
Soil Microorganisms ◽  
Docking Study ◽  
Chitinolytic Activity ◽  
Molecular Docking Study ◽  
Receptor Ligand ◽  
Docking Approach ◽  
Inhibitory Potential

Abstract A molecular docking study was undertaken using the programs SwissDock and PatchDock to assess the interactions of the bacterial chitinases belonging to the GH18 and GH19 families with two herbicides (chlorsulfuron and nicosulfuron) and two fungicides (difenoconazole and drazoxolon). Both molecular docking programs predict that all considered pesticides bind to the active sites of chitinases produced by soil microorganisms. There are correlations for predicted binding energy values for receptor-ligand complexes obtained using the two programs consolidating the prediction of the chitinases-pesticides interactions. The interactions of chitinases with pesticides involve the same residues as their interactions with known inhibitors suggesting the inhibitory potential of pesticides. Pesticides interact stronger with chitinases belonging to the GH18 family, their active sites reflecting higher polarity than those of the GH19 chitinases. Also, herbicides reveal a higher inhibitory potential to bacterial chitinases than fungicides.

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