Exploring the binding properties of agonists interacting with human TGR5 using structural modeling, molecular docking and dynamics simulations

RSC Advances ◽  
2015 ◽  
Vol 5 (19) ◽  
pp. 14202-14213 ◽  
Author(s):  
Thangaraj Sindhu ◽  
Pappu Srinivasan
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Type Ii Diabetes ◽  
Computational Study ◽  
Structural Modeling ◽  
Type Ii ◽  
Binding Properties ◽  
Pharmacological Target ◽  
Dynamics Simulations ◽  
Molecular Docking And Dynamics

TGR5, act as a potential pharmacological target in the treatment of type II diabetes. In the computational study, structural modeling and binding site prediction of TGR5 receptor was performed. Two well-known agonists of TGR5 used to investigate the mode and mechanism of binding.

scholarly journals Identification of Inhibitor Binding Site in Human Sirtuin 2 Using Molecular Docking and Dynamics Simulations

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e51429 ◽  
Author(s):  
Sugunadevi Sakkiah ◽  
Mahreen Arooj ◽  
Manian Rajesh Kumar ◽  
Soo Hyun Eom ◽  
Keun Woo Lee
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Inhibitor Binding ◽  
Dynamics Simulations ◽  
Molecular Docking And Dynamics

scholarly journals A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11171
Author(s):  
Neha Srivastava ◽  
Prekshi Garg ◽  
Prachi Srivastava ◽  
Prahlad Kishore Seth
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Site ◽  
Cinnamic Acid ◽  
Simulation Study ◽  
Computational Study ◽  
Dynamics Simulation ◽  
Receptor Protein ◽  
Novel Therapeutic

Background & Objectives The massive outbreak of Novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has turned out to be a serious global health issue worldwide. Currently, no drugs or vaccines are available for the treatment of COVID-19. The current computational study was attempted to identify a novel therapeutic inhibitor against novel SARS-CoV-2 using in silico drug discovery pipeline. Methods In the present study, the human angiotensin-converting enzyme 2 (ACE2) receptor was the target for the designing of drugs against the deadly virus. The 3D structure of the receptor was modeled & validated using a Swiss-model, Procheck & Errat server. A molecular docking study was performed between a group of natural & synthetic compounds having proven anti-viral activity with ACE2 receptor using Autodock tool 1.5.6. The molecular dynamics simulation study was performed using Desmond v 12 to evaluate the stability and interaction of the ACE2 receptor with a ligand. Results Based on the lowest binding energy, confirmation, and H-bond interaction, cinnamic acid (−5.20 kcal/mol), thymoquinone (−4.71 kcal/mol), and andrographolide (Kalmegh) (−4.00 kcal/mol) were screened out showing strong binding affinity to the active site of ACE2 receptor. MD simulations suggest that cinnamic acid, thymoquinone, and andrographolide (Kalmegh) could efficiently activate the biological pathway without changing the conformation in the binding site of the ACE2 receptor. The bioactivity and drug-likeness properties of compounds show their better pharmacological property and safer to use. Interpretation & Conclusions The study concludes the high potential of cinnamic acid, thymoquinone, and andrographolide against the SARS-CoV-2 ACE2 receptor protein. Thus, the molecular docking and MD simulation study will aid in understanding the molecular interaction between ligand and receptor binding site, thereby leading to novel therapeutic intervention.

Molecular docking and dynamics simulations of novel drug targets

2021 ◽  
pp. 79-131
Author(s):  
Jangampalli Adi Pradeepkiran ◽  
Manne Munikumar ◽  
Kanipakam Hema ◽  
Pradeep Natarajan ◽  
S.B. Sainath
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Dynamics Simulations ◽  
Novel Drug ◽  
Molecular Docking And Dynamics ◽  
Novel Drug Targets

scholarly journals Dasatinib–SIK2 Binding Elucidated by Homology Modeling, Molecular Docking, and Dynamics Simulations

ACS Omega ◽  
2021 ◽  
Author(s):  
Mingsong Shi ◽  
Lun Wang ◽  
Penghui Li ◽  
Jiang Liu ◽  
Lijuan Chen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Homology Modeling ◽  
Dynamics Simulations ◽  
Molecular Docking And Dynamics

An Explaining Theory for Diuretic-Induced-Diabetes Incidences

2018 ◽  
Author(s):  
Farah Yousef ◽  
Oussama Mansour ◽  
Jehad Herbali
Keyword(s):  
Diabetes Mellitus ◽  
Binding Site ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
The Other ◽  
Hypoglycemic Agents ◽  
Type Ii ◽  
Sulfonylurea Receptor ◽  
Lead Compound ◽  
Sulfonylurea Drugs

Many patients with hypertension are also suffering from Type II Diabetes Mellitus (TIIDM). Different studies argued the fact if these patients can use Hydrochlorothiazide (HCTZ) group or not to treat hyper-tension as these diuretics are accused with diuretic-induced diabetes especially Chlorthalidone and Bendroflumethiazide. As nothing is definite yet; in this paper, we are jotting down a new theory. In other words, we are seeking to study HCTZ interactions with sulfonylurea receptor Kir 6.2\SUR1 considering the chemical fact that HCTZ are also sulfonamide derivates like sulfonylurea drugs which are hypoglycemic agents used in the treatment of TIIDM. Therefore, we have studied in-silico 12 HCTZ compounds’ interactions with the binding site of sulfonylurea in its receptor Kir6.2\SUR1. Then, we compared the results to the interactions of Glibenclamide (GBM); a sulfonylurea agent, with the named receptor.  As a result, three compounds of this family (Chlorthalidone 1-1, Bendroflumethiazide 4-1, Metholazone 6-1) had bound to Kir6.2\SUR1 receptor in the same binding site of GBM. The rest members were almost close to the GBM binding site. These findings may explain the adverse effect that chlorthalidone and Bendroflumethiazide are accused with. We suggest that they are agonists for Kir6.1\SUR1 receptor, which results in decreasing insulin secretion from pancreas which consequences with hyper-glycemica. On the other hand, our results confirm that developing new anti hyperglycemia agents from HCTZ as a lead compound is also possible and promising.

Inhibition of the ATPase Domain of Human Topoisomerase IIa on HepG2 Cells by 1, 2-benzenedicarboxylic Acid, Mono (2-ethylhexyl) Ester: Molecular Docking and Dynamics Simulations

2019 ◽  
Vol 19 (6) ◽  
pp. 495-503 ◽  
Author(s):  
Jemimah Naine Selvakumar ◽  
Subathra Devi Chandrasekaran ◽  
George Priya C. Doss ◽  
Thirumal D. Kumar
Keyword(s):  
Molecular Docking ◽  
Hepg2 Cells ◽  
Flow Cytometric Analysis ◽  
Dynamics Simulation ◽  
Benzenedicarboxylic Acid ◽  
Bioassay Guided Fractionation ◽  
Marine Streptomyces ◽  
Dynamics Simulations ◽  
Molecular Docking And Dynamics

Background: The major attention has been received by the natural products in the prevention of diseases due to their pharmacological role. Objective: The major focus of the study was to search for highly potential anti-cancer compounds from marine Streptomyces sp. VITJS4 (NCIM No. 5574). Methods: Cytotoxic assay was examined by MTT assay on HepG2 cells. Bioassay-guided fractionation of the ethyl acetate extract from the fermented broth led to the isolation of the compound. The lead compound structure was elucidated by combined NMR and MS analysis, and the absolute configuration was assigned by extensive spectroscopic analysis. Results: On the basis of spectroscopic data, the compound was identified as 1, 2 benzenedicarboxylic acid, mono 2-ethylhexyl (BMEH). The compound exhibited in vitro anticancer potential against liver (HepG2) cancer cells. Based on the flow cytometric analysis, it was evident that the BMEH was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down-regulation of Bcl-2 family proteins, and activation of caspase-9 and 3. The molecular docking and dynamics simulation were performed to reveal the activity of the compound over a time period of 10ns. From the molecular dynamics studies, it was found that the stability and compactness were attained by the protein by means of the compound interaction. Conclusion: This study highlights our collaborative efforts to ascertain lead molecules from marine actinomycete. This is the first and foremost report to prove the mechanistic studies of the purified compound 1, 2-benzene dicarboxylic acid, mono(2-ethylhexyl) ester isolated from marine Streptomyces sp.VITJS4 against HepG2 cells.

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