scholarly journals Docking Molecular analysis of potential Aldosterone antagonists

2021 ◽  
Author(s):  
IVAN VITO FERRARI ◽  
Paolo Patrizio
Keyword(s):  
Binding Energy ◽  
Collecting Duct ◽  
Autodock Vina ◽  
Aldosterone Antagonists ◽  
Candidate Drug ◽  
Lamarckian Genetic Algorithm ◽  
Selective Analysis ◽  
First Time ◽  
Computational Drug Discovery ◽  
Screening Software

Background: Aldosterone antagonists (spironolactone, eplerenone) inhibit the action of aldosterone in the collecting duct; as such, these agents cause modest diuresis but inhibit potassium and hydrogen ion secretion. We report first time Potential Aldosterone antagonists by in Silico approach, using AutoDock Vina and AutoDock 4 (or MGL Tool), estimated with Pyrx and AM Dock Software, calculating three different important parameters: Binding Affinity ( kcal/mol), estimated Ki ( in nM units) and Ligand Efficiency ( L.E. in kcal/mol). After a selective analysis of over 1000 drugs, processed with Pyrx (a Virtual Screening software for Computational Drug Discovery) in the Ligand Binding site pocket of the protein ( ID PDB 2OAX Chain A:), we noticed high values of Binding Energy , about -13.55 kcal/mol estimated by AutoDock 4 with AM Dock Software, concluding that it could be an excellent candidate drug, compared to everyone else Aldosterone antagonists. Indeed, from the results of AutoDock Vina and AutoDock 4 ( or AutoDock 4.2 ), implemented with Lamarckian genetic algorithm, LGA, trough AMDock Software, our results of Binding Energy are very similar to the crystallized Spironolactone in PDB 2OAX Chain A protein.

scholarly journals An event excess observed in the deeply bound region of the 12C (K−, p) missing-mass spectrum

2020 ◽  
Vol 2020 (12) ◽  
Author(s):  
Yudai Ichikawa ◽  
Junko Yamagata-Sekihara ◽  
Jung Keun Ahn ◽  
Yuya Akazawa ◽  
Kanae Aoki ◽  
...  
Keyword(s):  
Mass Spectrum ◽  
Binding Energy ◽  
Decay Channel ◽  
Peak Shift ◽  
Bound State ◽  
Elastic Peak ◽  
Missing Mass ◽  
Decay Modes ◽  
Kaon Momentum ◽  
First Time

Abstract We have measured, for the first time, the inclusive missing-mass spectrum of the $^{12}$C$(K^-, p)$ reaction at an incident kaon momentum of 1.8 GeV/$c$ at the J-PARC K1.8 beamline. We observed a prominent quasi-elastic peak ($K^-p \rightarrow K^-p$) in this spectrum. In the quasi-elastic peak region, the effect of secondary interaction is apparently observed as a peak shift, and the peak exhibits a tail in the bound region. We compared the spectrum with a theoretical calculation based on the Green’s function method by assuming different values of the parameters for the $\bar{K}$–nucleus optical potential. We found that the spectrum shape in the binding-energy region $-300 \, \text{MeV} < B_{K} < 40$ MeV is best reproduced with the potential depths $V_0 = -80$ MeV (real part) and $W_0 = -40$ MeV (imaginary part). On the other hand, we observed a significant event excess in the deeply bound region around $B_{K} \sim 100$ MeV, where the major decay channel of $K^- NN \to \pi\Sigma N$ is energetically closed, and the non-mesonic decay modes ($K^- NN \to \Lambda N$ and $\Sigma N$) should mainly contribute. The enhancement is fitted well by a Breit–Wigner function with a kaon-binding energy of 90 MeV and width 100 MeV. A possible interpretation is a deeply bound state of a $Y^{*}$-nucleus system.

scholarly journals VIRTUAL SCREENING OF BETA-SECRETASE 1 (BACE1) INHIBITORS IN THE INDONESIAN HERBAL DATABASE AS USING AUTODOCK AND AUTODOCK VINA

2017 ◽  
Vol 10 (17) ◽  
pp. 148
Author(s):  
Asti Anna Tanisa ◽  
Rezi Riadhi
Keyword(s):  
Binding Energy ◽  
Virtual Screening ◽  
Cellular Response ◽  
Senile Plaque ◽  
Area Under The Curve ◽  
Neuronal System ◽  
Operating Characteristics ◽  
Autodock Vina ◽  
Beta Secretase ◽  
The Brain

  Objective: Alzheimer’s is a neurodegenerative disease caused by the accumulation of senile plaque in the brain that affects neuronal system leading to a less sensitive cellular response from neurons. Previous research has found that beta-secretase 1 (BACE1) plays an important role in the senile plaque formation, become a target in Alzheimer’s medication.Methods: In this study, virtual screening of BACE1 inhibitors on the Indonesian Herbal Database was done using AutoDock and AutoDock Vina. The screening was validated using the directory of useful decoys: Enhanced database. Parameters for validation process of AutoDock and AutoDock Vina are enrichment factor (EF), receiver operating characteristics, and area under the curve (AUC).Results: The dimensions of grid boxes were 30×30×30 (AutoDock) and 11.25×11.25×11.25 (AutoDock Vina). The EF 1% and AUC values obtained from the AutoDock are 7.74 and 0.73, respectively, and in the AutoDock Vina are 4.6 and 0.77, respectively. Based on the virtual screening results, the top six compounds obtained using AutoDock (binding energy ranging from −7.84 kcal/mol to −8.79 kcal/mol) include: Azadiradione, cylindrin, lanosterol, sapogenin, simiarenol, and taraxerol. The top seven compounds (binding energy ranging from −8.8 kcal/mol to −9.4 kcal/mol) obtained using AutoDeck Vina include: Bryophyllin A, diosgenin, azadiradione, sojagol, beta-amyrin, epifriedelinol, and jasmolactone C.Conclusions: Only azadiradione was obtained from the virtual screening conducted using both types of software; it interacts with the active region in BACE1 at residue Trp 76 (AutoDock result) and Thr 232 (AutoDock Vina result).  

Xps Analysis of the Sapphire Surface as a Function of High Temperature Vacuum Annealing

1989 ◽  
Vol 159 ◽  
Author(s):  
E.D. Richmond
Keyword(s):  
High Temperature ◽  
Binding Energy ◽  
Photoelectron Spectroscopy ◽  
Vacuum Annealing ◽  
Xps Analysis ◽  
Chemical Changes ◽  
Cleaning Procedure ◽  
Sapphire Surface ◽  
X Ray ◽  
First Time

ABSTRACTFor the first time the (1102) surface of sapphire has been investigated by X-ray photoelectron spectroscopy to ascertain chemical changes resulting from annealing in vacuum at 1300° C and 1450° C. As received substrates had a substantial surface C contaminant. For substrates that were chemically cleaned before inserting them into the MBE system no trace of carbon is detected. A residual flourine contaminant results from the cleaning procedure and is desorbed by the vacuum annealing. Spectra of annealed substrates are compared to the unannealed chemically cleaned substrates. The annealed substrates exhibit 0.4 to 0.5 eV shift to higher binding energy of the Al peak and a 0.3 eV shift to higher binding energy of the O peak. In addition, a 2% depletion of oxygen from the surface occurs.

Abstract P301: Renal Expression of Collectrin (TMEM27) is Downregulated During Angiotensin II-induced Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sylvia Cechova ◽  
Pei-Lun Chu ◽  
Joseph Gigliotti ◽  
Thu H Le
Keyword(s):  
Angiotensin Ii ◽  
Catalytic Domain ◽  
Collecting Duct ◽  
Amino Acid Transporters ◽  
Ang Ii ◽  
Salt Loading ◽  
Transmembrane Glycoprotein ◽  
First Time ◽  
Renal Expression

Collectrin ( Tmem27 ) is transmembrane glycoprotein with homology to ACE-2, but lacks any catalytic domain. It plays a key role as a chaperone of amino acid transporters, and is abundantly expressed in the kidney in the proximal tubules and collecting duct. Deletion of collectrin in the mouse results in hypertension (HTN) at baseline and augmented salt-sensitivity that are associated with decreased renal nitric oxide and increased superoxide levels. During high salt diet, renal expression of collectrin is upregulated, suggesting an adaptive homeostatic response to salt loading. Here, we queried whether the expression of collectrin is regulated by angiotensin II (Ang II). Wild-type 129S6 mice were made hypertensive with Ang II osmotic minipump @ 600 ng/kg/min x 2 weeks, and were compared to age-matched untreated WT 129 mice. Shown in Fig. 1 , renal mRNA expression of collectrin is significantly reduced after 2 weeks of Ang II (Panel A). Immunostaining shows collectrin protein level is also significantly diminished to near undetectable level (Panel B). We show for the first time that Ang II regulates the expression of collectrin, suggesting that the action of Ang II on blood pressure may be mediated, in part, through the downregulation of collectrin. Further studies are needed to determine the effect of AT 1 and AT 2 receptor signaling on renal expression of collectrin during Ang II-HTN in vivo.

Downregulation of SGK1 by nucleotides in renal tubular epithelial cells

2007 ◽  
Vol 293 (5) ◽  
pp. F1751-F1757 ◽  
Author(s):  
Liuzhe Li ◽  
Charles S. Wingo ◽  
Shen-Ling Xia
Keyword(s):  
Epithelial Cells ◽  
Purinergic Receptors ◽  
Kinase Activity ◽  
Purinergic Signaling ◽  
Collecting Duct ◽  
Collecting Duct Cells ◽  
Renal Collecting Duct ◽  
Renal Tubular ◽  
First Time ◽  
Dependent Pathway

This study determined whether nucleotides that bind to purinergic receptors (P2R) regulate the expression or function of serum- and glucocorticoid-inducible kinase-1 (SGK1) in mouse renal inner medullar collecting duct cells (mIMCD-3). The SGK1 protein was detected by Western blotting. A significant reduction of cytosolic SGK1 expression was observed in the cells pretreated with P2R agonist adenosine 5′- O-(3-thiotriphosphate) (ATPγS), and the reduction could be reversed by P2R antagonists. This reduction was also observed in cells that were pretreated with agonists for P2R subtypes. Using ELISA, we observed a reduced SGK1 kinase activity in ATPγS-pretreated cells. This effect was reversed by P2R antagonists. Furthermore, an increase of SGK1 kinase activity in aldosterone-pretreated cells was suppressed by ATPγS. These studies demonstrate for the first time that SGK1 can be downregulated by nucleotides in renal collecting duct epithelial cells, likely via the activation of P2R, and suggest that activation of renal purinergic signaling regulates a SGK1-dependent pathway that is known to modulate ion transport in the renal collecting duct.

scholarly journals Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention

2020 ◽  
Author(s):  
Atala B. Jena ◽  
Namrata Kanungo ◽  
Vinayak Nayak ◽  
G.B.N. Chainy ◽  
Jagneshwar Dandapat
Keyword(s):  
Binding Energy ◽  
Preventive Intervention ◽  
Computational Study ◽  
Protein S ◽  
Cell Receptor ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Host Cell Receptor ◽  
Recent Outbreak ◽  
First Time

Abstract The recent outbreak of the coronavirus (2019n-CoV) is an unprecedented threat for human health throughout the globe. In this regards development of a suitable intervention is the need of the hour. The viral spike protein (S-Protein) and the cognate host cell receptor ACE2 can prove to be effective. Here, through computational approaches we have reported two polyphenols, Catechin and Curcumin which have dual binding affinity i.e both the molecule binds to viral S-protein and as well as ACE2. Catechin binds with S-protein and ACE2 with binding energy of -10.5 Kcal/mol and -8.9 Kcal/mol, respectively. Catechin binds with a greater affinty than that of curcumin which has a binding energy of -7.9Kcal/mol and - 7.8Kcal/mol for S-protein and ACE2, respectively. While curcumin gets bound directly to receptor binding domain (RBD) of viral S-protein, catechin binds to near proximity of RBD sequence of S-protein. Molecular simulation study demonstrates that curcumin directly binds with RBD site of S-protein during 40-100ns. In contrast, catechin binds with S-protein near the RBD site and causes fluctuation in the amino acids present in the RBD and it’s near proximity. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols, for therapeutic/preventive intervention.

scholarly journals Rapid Prediction of Possible Inhibitors for SARS-CoV-2 Main Protease using Docking and FPL Simulations

2020 ◽  
Author(s):  
Pham Minh Quan ◽  
Khanh B. Vu ◽  
T. Ngoc Han Pham ◽  
Le Thi Thuy Huong ◽  
Linh Hoang Tran ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Global Health ◽  
Effective Treatment ◽  
Correlation Coefficients ◽  
Autodock Vina ◽  
Main Protease ◽  
Rapid Prediction ◽  
Global Health Issue ◽  
Potential Inhibitors ◽  
First Time

Appearance for the first time from Wuhan, China, the SARS-CoV-2 rapidly outbreaks worldwide and causes a serious global health issue. The effective treatment for SARS-CoV-2 is still unavailable. Therefore, in this work, we have tried to rapidly predict a list of potential inhibitors for SARS-CoV-2 main protease (Mpro) using a combination of molecular docking and fast pulling of ligand (FPL) simulations. The approaches were initially validated over a set of eleven available inhibitors. Both Autodock Vina and FPL calculations adopted good consistent results with the respective experiment with correlation coefficients of R_Dock=0.72 ± 0.14 and R_W = -0.76 ± 0.10, respectively. The combined approaches were then utilized to predict possible inhibitors, which were selected from a ZINC15 sub-database, for SARS-CoV-2 Mpro. Twenty compounds were suggested to be able to bind well to SARS-CoV-2 Mpro. The obtained results probably lead to enhance COVID-19 therapy.

scholarly journals Novel Human Kidney Cell Subsets Identified by Mux-Seq

2020 ◽  
Author(s):  
Andrew W. Schroeder ◽  
Swastika Sur ◽  
Priyanka Rashmi ◽  
Izabella Damm ◽  
Arya Zarinsefat ◽  
...  
Keyword(s):  
Single Cell ◽  
Collecting Duct ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Cost Effective ◽  
Cell Types ◽  
Single Cell Rna Sequencing ◽  
Proximal Tubular ◽  
Highly Correlated ◽  
First Time

AbstractBackgroundThe kidney is a highly complex organ that performs multiple functions necessary to maintain systemic homeostasis, with complex interplay from different kidney sub-structures and the coordinated response of diverse cell types, few known and likely many others, as yet undiscovered. Traditional global sequencing techniques are limited in their ability to identify unique and functionally diverse cell types in complex tissues.MethodsHerein we characterize over 45,000 cells from 10 normal human kidneys using unbiased single-cell RNA sequencing. We also apply, for the first time, an approach of multiplexing kidney samples (Mux-Seq), pooled from different individuals, to save input sample amount and cost. We applied the computational tool Demuxlet to assess differential expression across multiple individuals by pooling human kidney cells for scRNA sequencing, utilizing individual genetic variability to determine the identity of each cell.ResultsMultiplexed droplet single-cell RNA sequencing results were highly correlated with the singleplexed sample run data. One hundred distinct cell cluster populations in total were identified across the major cell types of the kidney, with varied functional states. Proximal tubular and collecting duct cells were the most heterogeneous, displaying multiple clusters with unique ontologies. Novel proximal tubular cell subsets were identified with regenerative potential. Trajectory analysis demonstrated evolution of cell states between intercalated and principal cells in the collecting duct.ConclusionsHealthy kidney tissue has been successfully analyzed to detect all known renal cell types, inclusive of resident and infiltrating immune cells in the kidney. Mux-Seq is a unique method that allows for rapid and cost-effective single cell, in depth, transcriptional analysis of human kidney tissue.Significance StatementUse of renal biopsies for single cell transcriptomics is limited by small tissue availability and batch effects. In this study, we have successfully employed the use of Mux-Seq for the first time in kidney. Mux-Seq allows the use of single cell technology at a much more cost-effective manner by pooling samples from multiple individuals for a single sequencing run. This is even more relevant in the case of patient biopsies where the input of tissue is significantly limited. We show that the data from overlapping tissue samples are highly correlated between Mux-Seq and traditional Singleplexed RNA seq. Furthermore, the results from Mux-Seq of 4 pooled samples are highly correlated with singleplexed data from 10 singleplex samples despite the inherent variability among individuals.

Proton pump-rich cell secretes acid in skin of zebrafish larvae

2006 ◽  
Vol 290 (2) ◽  
pp. C371-C378 ◽  
Author(s):  
Li-Yih Lin ◽  
Jiun-Lin Horng ◽  
Joseph G. Kunkel ◽  
Pung-Pung Hwang
Keyword(s):  
Proton Pump ◽  
Intact Animal ◽  
Collecting Duct ◽  
Suitable Model ◽  
Cell Type ◽  
Distal Nephron ◽  
Noninvasive Technique ◽  
Acid Load ◽  
First Time

The mammalian kidney excretes its metabolic acid load through the proton-transporting cells, intercalated cells, in the distal nephron and collecting duct. Fish excrete acid through external organs, gill, or skin; however, the cellular function is still controversial. In this study, molecular and electrophysiological approaches were used to identify a novel cell type secreting acid in skin of zebrafish ( Danio rerio) larvae. Among keratinocytes covering the larval surface, novel proton-secreting ionocytes, proton pump (H+-ATPase)-rich cells, were identified to generate strong outward H+ flux. The present work demonstrates for the first time, with a noninvasive technique, H+-secreting cells in an intact animal model, the zebrafish, showing it to be a suitable model in which to study the functions of vertebrate transporting epithelia in vivo.

scholarly journals STRUCTURE PREDICTION AND IN SILICO DESIGNING OF DRUGS AGAINST KALLIKREIN PROTEIN 12

2017 ◽  
Vol 9 (2) ◽  
pp. 64
Author(s):  
Manish Devgan
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Structure Prediction ◽  
Docking Studies ◽  
Receptor Protein ◽  
Loop Modeling ◽  
Autodock Vina ◽  
Potential Therapeutic Target ◽  
Plot Analysis ◽  
In Silico Molecular Docking

Objective: Human Kallikrein protein 12 (hK12) might serve as a novel diagnostic and prognostic biomarker, as well as a potential therapeutic target, in gastric cancer.Methods: In this work, a theoretical model of hK12 receptor protein was generated using the concepts of homology modeling and loop modeling. The resulting model was validated with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against hK12 receptor protein using AutoDock Vina in PyRx 0.8. The structure of ligand DB04786 (Suramin), with least binding energy, was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 16 new ligands.Results: The results indicated that the ligand10 bears the minimum binding energy (-12.3 Kcal/mol) with the target protein and thus the prospects of binding are high. The results also clearly demonstrated that the in silico molecular docking studies of selected ligands, i.e., suramin, ligands 5, 6, 10 and 16 with hK12 protein exhibited favourable binding interactions and warranted.Conclusion: Further studies needed for the development of potent inhibitors for the overexpression of hK12 protein making the management of gastric cancer more efficient.

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