scholarly journals Molecular docking studies of 1, 3, 4 oxadiazoles Derivatives as anti-convulsive agents

2020 ◽  
Vol 8 (1) ◽  
pp. 151-179
Author(s):  
Sachin Jangra ◽  
Sachin Kumar ◽  
Manjusha Choudhary
Keyword(s):  
Amino Acids ◽  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Site ◽  
Gabaa Receptor ◽  
Small Molecule ◽  
Future Research ◽  
Computational Technique ◽  
Standard Drug ◽  
Hydrogen Bond Interactions

Molecular docking is a computational technique that places a small molecule (ligand) in the binding site of its macromolecular target (receptor) and estimates its binding affinity. The present study attempted the high throughput in-silico screening of 65 compounds docked with the GABAA receptor (PDB ID: 4COF) using Molegro virtual docker (6.0). Out of these 65 compounds, 17 compounds showed very good mol dock score in ranging between -66.344 & -102.653. Ethosuximide and Carbamazepine drugs was used as a standard drug which showed mol dock score -50.6357 & -58.5047 respectively. Most of test compounds demonstrated excellent number of hydrogen bond interactions viz compounds 33, 38, 39, 45, 47, 53, 54, 59, 61, 62, 63, 64 & 65 which showed 7 to 11 number of hydrogen bond interactions as compared to standard drug interactions values 6 & 5 respectively and also showed the interaction with same amino acids Glu52, Ser51and Val53 and some other amino acids Asn54, Thr58 and Thr133 also showed very acceptable bond length less than 3.91Å. The obtained results indicated that all studied ligands have similar position and orientation inside the putative binding site of GABAA receptor (PDB ID: 4COF) which reveals a large space bounded by a membrane-binding domain which serves as an entry channel for substrate to the active site. In addition, the affinity of any small molecule can be considered as a unique tool in the field of drug design and offer prospective in future research to develop a potent anticonvulsant agent.

scholarly journals In-silico Investigation of the Interaction between Beta-class Glutathione S-Transferase and Five Antibiotics, namely; Ampicillin, Tetracycline, Chloramphenicol, Ciprofloxacin and Cephalexin

2021 ◽  
Vol 25 (4) ◽  
pp. 497-502
Author(s):  
D. Shehu ◽  
S Danlami ◽  
M. Ya’u ◽  
A. Babandi ◽  
H.M. Yakasai ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antibiotic Resistance ◽  
Molecular Docking ◽  
Binding Site ◽  
Substrate Binding ◽  
Docking Study ◽  
Glutathione S Transferase ◽  
Molecular Docking Study ◽  
Substrate Binding Site ◽  
Glutathione S Transferases

Glutathione s-transferases(GSTs) are enzymes involved in the conjugation and deactivation of various xenobiotics including drugs. Thisin-silico study was undertaken in order to investigate the interaction between beta-class glutathione s-transferase and five selected antibiotics, namely; ampicillin, tetracycline, chloramphenicol, ciprofloxacin and cephalexin using molecular docking study. RaptorX server was used to predict the amino acids involved at the binding sitewhile molecular docking study was employed in order to investigate the binding interactions.RaptorX predicted several amino acids which were different from the ones observed in molecular docking because of the variability in the substrate binding site of GSTs however, all the amino acids predicted by RaptorX were also found to be involved in the GSH binding.Lys107, Phe109, Ser110, Leu113, Trp114, His115 and Arg123, Leu168 were the amino acids involved in the binding of various antibiotics to the substrate binding site of the protein while Ala9, Cys10, Leu32, Tyr51, Val52, Pro53, Glu65 and Ala66were involved in the binding of the co-substrate GSH to the binding site of the protein. The results indicated that all the antibiotics showed a good binding affinity with the beta class GST and are therefore capable of deactivating the drugs. With these, finding a beta class GST inhibitors alongside antibiotics during a treatment of diseases will be of beneficial in the current fight against antibiotic resistance.

scholarly journals Prediction of the Anxiolytic Action Mediated by the GABA A Receptor by the Molecular Docking Method

2020 ◽  
Vol 6 (5) ◽  
pp. 38-45
Author(s):  
T. Gendugov ◽  
A. Glushko ◽  
A. Chiriapkin ◽  
V. Chiriapkin
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Site ◽  
Computational Experiment ◽  
Gaba A ◽  
High Affinity ◽  
Docking Method ◽  
Benzodiazepine Binding ◽  
Docking Energy ◽  
Molecular Docking Method

The article considers the study in silico of the affinity of 3-[2-oxo-2-(4-phenyl-1-piperazinyl)ethyl]-4(3H)-quinazolinone (VMA-10-21 compound) to the benzodiazepine binding site of the GABA А receptor by molecular docking method. The computational experiment was carried out using a set of Autodock programs. As a result, the method for predicting the affinity of the simulated compounds to the benzodiazepine binding site of the GABA A receptor was developed. The highest correlation coefficient between the pKi value and the average docking energy in the benzodiazepine binding site (0.54) was obtained using a set of amino acids Tyr 58 and Tyr 159. The predicted Ki value of the VMA-10-21 compound is 2.864 nM, which suggests a high affinity of the studied compound to this receptor.

scholarly journals P3-293: Investigation of the critical amino acids in the BACE1 binding site that interact with small molecule inhibitors using a novel radioligand and X-ray crystallography

2009 ◽  
Vol 5 (4S_Part_14) ◽  
pp. P429-P429
Author(s):  
Warren D. Hirst ◽  
Katie Kubek ◽  
Jonathan Bard ◽  
James Turner ◽  
Kristi Fan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Binding Site ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
X Ray ◽  
X Ray Crystallography

scholarly journals Interaction of Irbesartan with Bovine Hemoglobin Using Spectroscopic Techniques and Molecular Docking

2012 ◽  
Vol 27 ◽  
pp. 119-128 ◽  
Author(s):  
Ai-Ping Yang ◽  
Mei-Hua Ma ◽  
Xiao-Hua Li ◽  
Mao-Yun Xue
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Site ◽  
Binding Free Energy ◽  
Protein Secondary Structure ◽  
Cd Spectroscopy ◽  
Electrostatic Energy ◽  
Bovine Hemoglobin ◽  
Spectroscopic Techniques ◽  
Hydrogen Bond Formation

The binding of irbesartan to bovine hemoglobin (BHb) has been investigated for the first time by using UV-Vis absorption, fluorescence, circular dichroism (CD), and molecular docking. The binding site numbernand binding constantKwere calculated to be 1 and , respectively. The alternations of protein secondary structure in the presence of irbesartan was demonstrated using CD spectroscopy. Furthermore, molecular docking indicated that irbesartan could bind to the site 2 of BHb. The analysis of the binding site of irbesartan within the BHb molecule suggested that hydrophobic interaction, hydrogen bond formation, and electrostatic interaction could account for the binding of irbesartan. The hydrogen bond of irbesartan with His87 in the C chain of BHb has been formed. The electrostatic energy, van der Waals energy, and binding free energy were calculated to be −460.3, −224.2, and−684.5 kcal, respectively.

scholarly journals Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti-SARS-CoV2 Protease Inhibitor

2020 ◽  
Vol 14 (10) ◽  
pp. 52
Author(s):  
Usman Abdulfatai ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Docking Simulation ◽  
Binding Energies ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Molecular Docking Analysis

In this present investigation, simulated molecular docking study of chloroquine and hydroxychloroquine compounds were investigated on the SARS-CoV2 enzyme to determine the types of amino acids responsible for the biochemical reaction at the binding site. A structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARS-CoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the management of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1 kcal/mol and -6.8 kcal/mol respectively. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to formed hydrogen and conventional interactions with the binding site of SARS-CoV2 protease through amino acids such as Glutamic acid (GLU166), Glycine (GLY143), Phenylalanine (PHE140), Asparagine (ASN142), Histidine (HIS163), His (HIS172, HIS41, HIS163), Leucine (LEU41, LEU27), Glycine (GLY143), Glutamine (GLN189), Methionine (MET49, MET165), Serine (SER 46), Cysteine (CYS145) and Threonine (THR25). With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease’ binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for biochemical action on SARS-CoV2 protease.

scholarly journals MOLECULAR DOCKING OF ANTITRYPANOSOMAL INHIBITORS FROM EUCALYPTUS TERETICORNIS FOR SLEEPING SICKNESS

2019 ◽  
pp. 191-195
Author(s):  
AARTHI RASHMI B ◽  
HARISHCHANDER A ◽  
PRIYANKA K ◽  
VASANTH NIRMAL BOSCO
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Binding Energy ◽  
Sleeping Sickness ◽  
Betulonic Acid ◽  
Eucalyptus Tereticornis ◽  
Hydrogen Bond Interaction ◽  
Hydrogen Bond Interactions ◽  
Bond Interaction ◽  
Pure Compounds

Objectives: This study aims to investigate the antitrypanosomal inhibitors of Eucalyptus tereticornis for sleeping sickness through molecular docking and studies on Absorption distribution metabolism excursion and toxicology (ADMET). Methods: In silico molecular docking in ArgusLab software and ADMET analysis in AdmetSAR software was performed for the antitrypanosomal inhibitors of E. tereticornis for sleeping sickness. Results: Interactions were studied for the ten proteins responsible for sleeping sickness with the 50 antitrypanosomal inhibitors of E. tereticornis. Docking was performed to see the interaction and the best binding energy of compounds with the proteins involved in sleeping sickness. The docking scores were highest for betulonic acid with −15.66 kcal/mol followed by euglobal with −12.24 kcal/mol, B-pinene with −10.313 kcal/mol, A-pinene with −10.3418 kcal/mol, and the least docking score for P-cymene with −10.6045 kcal/mol. Docking results showed that only betulonic acid and euglobal showed that hydrogen bond interaction was as b-pinene, a-pinene, and p-cymene yielded no hydrogen bond interactions so we will be taking the former docking results for further studies. The best docking result was shown by betulonic acid with trypanothione reductase giving binding energy of −15.66 kcal/mol with hydrogen bond interaction of 2.9, so this result was taken for further analysis. Conclusion: The results of the compound extracted from E. tereticornis will become physiological relevant only when (i) the pure compounds of this plant is available in large quantities; (ii) the Eucalyptus is biochemically stabilized to avoid degradation and enhance absorption in the gastrointestinal tract; and (iii) special delivery methods for this drug to reach the areas of treatment. In this work, the efficacy of E. tereticornis to act against trypanosomal protein was initiated and thus further research in this process would help us to take full advantage of the remedial effects of the compounds extracted from this plant.

scholarly journals Biological Regulatory Network (BRN) Analysis and Molecular Docking Simulations to Probe the Modulation of IP3R Mediated Ca2+ Signaling in Cancer

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 34
Author(s):  
Humaira Ismatullah ◽  
Ishrat Jabeen ◽  
Muhammad Tariq Saeed
Keyword(s):  
Cell Proliferation ◽  
Hydrogen Bond ◽  
Cell Death ◽  
Molecular Docking ◽  
Cancer Progression ◽  
Regulatory Network ◽  
Hydroxyl Group ◽  
Docking Simulations ◽  
Cellular Processes ◽  
Hydrogen Bond Interactions

Inositol trisphosphate receptor (IP3R) mediated Ca+2 signaling is essential in determining the cell fate by regulating numerous cellular processes, including cell division and cell death. Despite extensive studies about the characterization of IP3R in cancer, the underlying molecular mechanism initiating the cell proliferation and apoptosis remained enigmatic. Moreover, in cancer, the modulation of IP3R in downstream signaling pathways, which control oncogenesis and cancer progression, is not well characterized. Here, we constructed a biological regulatory network (BRN), and describe the remodeling of IP3R mediated Ca2+ signaling as a central key that controls the cellular processes in cancer. Moreover, we summarize how the inhibition of IP3R affects the deregulated cell proliferation and cell death in cancer cells and results in the initiation of pro-survival responses in resistance of cell death in normal cells. Further, we also investigated the role of stereo-specificity of IP3 molecule and its analogs in binding with the IP3 receptor. Molecular docking simulations showed that the hydroxyl group at R6 position along with the phosphate group at R5 position in ‘R’ conformation is more favorable for IP3 interactions. Additionally, Arg-266 and Arg-510 showed π–π and hydrogen bond interactions and Ser-278 forms hydrogen bond interactions with the IP3 binding site. Thus, they are identified as crucial for the binding of antagonists.

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