Assessing the Prediction Quality of the Anti-SARS-CoV-2 Activity Using the D3Targets-2019-nCoV Web Service

2020 ◽  
Vol 3 (4) ◽  
pp. e00140
Author(s):  
N.S. Ionov ◽  
P.V. Pogodin ◽  
V.V. Poroikov
Keyword(s):  
Molecular Docking ◽  
Web Service ◽  
Scoring Function ◽  
Chemical Compounds ◽  
Structural Similarity ◽  
Similarity Score ◽  
Test Set ◽  
Target Proteins ◽  
Similarity Assessment

The D3Targets-2019-nCoV web service predicting the interaction of chemical compounds with SARS-CoV-2 virus proteins and human proteins involved in the pathogenesis of COVID-19 by structural similarity and molecular docking was evaluated. The quality of the prediction was assessed as a balanced accuracy, which was calculated based on the results of the prediction for the structures of chemical compounds from the test set we compiled. The test set consisted of 35 active and 59 inactive molecules, including compounds with the experimetnaly confirmed absence of activity against the selected targets and compounds active against SARS-CoV-2 targets, not presented in the CoViLigands database. The authors of the analyzed web service did not indicate the thresholds for the values of the similarity score and the docking scoring function, using which it would be possible to reliably divide the compounds into active and inactive with respect to target proteins. Therefore, we assessed the balanced accuracy of the predictive methods D3Targets-2019-nCoV at various thresholds for cutting off active substances from inactive ones. Using our test set it was found that the highest value of balanced accuracy (0.59) was achieved when choosing active molecules based on the results of 2D similarity assessment (cutoff threshold was 46%). Assessment of 3D similarity did not allow achieving balanced accuracy values exceeding 0.5. It is shown that using the 2Dх3D integral similarity assessment recommended by the authors, the maximum value of the balanced accuracy 0.57 was achieved at a threshold of 31%. The calculated balanced accuracy for molecular docking results does not exceed 0.51. On the case study for the tideglusib, it was shown that the values of the scoring function for two target proteins, the activity against which was confirmed in the experiment (3CLpro and GSK3B), do not differ significantly from the values of the scoring function for the remaining 44 targets were not confirmed.

Web Services Architecture Model to Support Distributed Systems

2019 ◽  
Vol 54 (6) ◽  
Author(s):  
Sawsan Ali Hamid ◽  
Rana Alauldeen Abdalrahman ◽  
Inam Abdullah Lafta ◽  
Israa Al Barazanchi
Keyword(s):  
Web Services ◽  
Web Service ◽  
Distributed System ◽  
Modern Technology ◽  
Service Description ◽  
Architecture Model ◽  
Software Applications ◽  
Evolving Model ◽  
The Web

Recently, web services have presented a new and evolving model for constructing the distributed system. The meteoric growth of the Web over the last few years proves the efficacy of using simple protocols over the Internet as the basis for a large number of web services and applications. Web service is a modern technology of web, which can be defined as software applications with a programmatic interface based on Internet protocol. Web services became common in the applications of the web by the help of Universal, Description, Discovery and Integration; Web Service Description Language and Simple Object Access Protocol. The architecture of web services refers to a collection of conceptual components in which common sets of standard can be defined among interoperating components. Nevertheless, the existing Web service's architecture is not impervious to some challenges, such as security problems, and the quality of services. Against this backdrop, the present study will provide an overview of these issues. Therefore, it aims to propose web services architecture model to support distributed system in terms of application and issues.

scholarly journals GNINA 1.0: molecular docking with deep learning

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Andrew T. McNutt ◽  
Paul Francoeur ◽  
Rishal Aggarwal ◽  
Tomohide Masuda ◽  
Rocco Meli ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Root Mean Square ◽  
Root Mean Square Deviation ◽  
Computational Cost ◽  
Scoring Function ◽  
Binding Pocket ◽  
Protein Docking ◽  
Mean Square ◽  
Mean Square Deviation ◽  
Autodock Vina

AbstractMolecular docking computationally predicts the conformation of a small molecule when binding to a receptor. Scoring functions are a vital piece of any molecular docking pipeline as they determine the fitness of sampled poses. Here we describe and evaluate the 1.0 release of the Gnina docking software, which utilizes an ensemble of convolutional neural networks (CNNs) as a scoring function. We also explore an array of parameter values for Gnina 1.0 to optimize docking performance and computational cost. Docking performance, as evaluated by the percentage of targets where the top pose is better than 2Å root mean square deviation (Top1), is compared to AutoDock Vina scoring when utilizing explicitly defined binding pockets or whole protein docking. Gnina, utilizing a CNN scoring function to rescore the output poses, outperforms AutoDock Vina scoring on redocking and cross-docking tasks when the binding pocket is defined (Top1 increases from 58% to 73% and from 27% to 37%, respectively) and when the whole protein defines the binding pocket (Top1 increases from 31% to 38% and from 12% to 16%, respectively). The derived ensemble of CNNs generalizes to unseen proteins and ligands and produces scores that correlate well with the root mean square deviation to the known binding pose. We provide the 1.0 version of Gnina under an open source license for use as a molecular docking tool at https://github.com/gnina/gnina.

scholarly journals Prospect into therapeutic potentials of Moringa oleifera phytocompounds against cancer upsurge: de novo synthesis of test compounds, molecular docking, and ADMET studies

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
P. M. Aja ◽  
P. C. Agu ◽  
E. M. Ezeh ◽  
J. N. Awoke ◽  
H. A. Ogwoni ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Cancer Chemotherapy ◽  
Moringa Oleifera ◽  
De Novo ◽  
Gas Chromatography Mass Spectrometry ◽  
Molecular Docking Study ◽  
Cancer Proliferation ◽  
Target Proteins ◽  
Potential Inhibitors

Abstract Background Cancer chemotherapy is difficult because current medications for the treatment of cancer have been linked to a slew of side effects; as a result, researchers are tasked with developing greener cancer chemotherapies. Moringa oleifera has been reported with several bioactive compounds which confirm its application for various ailments by traditional practitioners. In this study, we aim to prospect the therapeutic potentials of M. oleifera phytocompounds against cancer proliferation as a step towards drug discovery using a computational approach. Target proteins: dihydrofolate reductase (DHFR) and B-Cell Lymphoid-2 (BCL-2), were retrieved from the RCSB PDB web server. Sixteen and five phytocompounds previously reported in M. oleifera leaves (ML) and seeds (MS), respectively, by gas chromatography–mass spectrometry were synthesized and used in the molecular docking study. For accurate prediction of binding sites of the target proteins; standard inhibitors, Methotrexate (MTX) for DHFR, and Venetoclax (VTC) for BCL-2, were docked together with the test compounds. We further predicted the ADMET profile of the potential inhibitors for an insight into their chance of success as candidates in drug discovery. Results Results for the binding affinities, docking poses, and the interactions showed that ML2, ML4-6, ML8-15, and MS1-5 are potential inhibitors of DHFR and BCL-2, respectively. In the ADMET profile, ML2 and ML4 showed the best drug-likeness by non-violation of Lipski Rule of Five. ML4-6, ML8, ML11, ML14-15, and MS1, MS3-5 exhibit high GI absorption; ML2, ML4-6, ML8, MS1, and MS5 are blood–brain barrier permeants. ML2, ML4, ML9, ML13, and MS2 do not interfere with any of the CYP450 isoforms. The toxicity profile showed that all the potential inhibitors are non-carcinogenic and non-hERG I (human ether-a-go-go related gene I) inhibitors. ML4, ML11, and MS4 are hepatotoxic and ML7, ML10, and MS4 are hERG II inhibitors. A plethora of insights on the toxic endpoints and lethal concentration values showed that ML5, ML13, and MS2 are comparatively less lethal than other potential inhibitors. Conclusion This study has demonstrated that M. oleifera phytocompounds are potential inhibitors of the disease proteins involved in cancer proliferation, thus, an invaluable step toward the discovery of cancer chemotherapy with lesser limitations.

scholarly journals The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1025
Author(s):  
Ahmed Alalaiwe ◽  
Jia-You Fang ◽  
Hsien-Ju Lee ◽  
Chun-Hui Chiu ◽  
Ching-Yun Hsu
Keyword(s):  
Molecular Docking ◽  
Fatty Acid Synthase ◽  
Structural Similarity ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

scholarly journals Antioxidant Therapy in Inflammatory Bowel Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 412
Author(s):  
Katarzyna Dziąbowska-Grabias ◽  
Małgorzata Sztanke ◽  
Przemysław Zając ◽  
Michał Celejewski ◽  
Katarzyna Kurek ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Nitrosative Stress ◽  
Treatment Options ◽  
Chemical Compounds ◽  
Continuous Increase ◽  
Public Health Burden ◽  
Bowel Diseases ◽  
Significant Public Health ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are a group of chronic, incurable diseases of the digestive tract, the etiology of which remains unclear to this day. IBD result in significant repercussions on the quality of patients’ life. There is a continuous increase in the incidence and prevalence of IBD worldwide, and it is becoming a significant public health burden. Pharmaceuticals commonly used in IBD management, for example, mesalamine, sulfasalazine, corticosteroids, and others, expose patients to diverse, potentially detrimental side effects and frequently do not provide sufficient disease control. The chronic inflammation underlies the etiology of IBD and closely associates with oxidative/nitrosative stress and a vast generation of reactive oxygen/nitrogen species. Relative to this, several substances with antioxidant and anti-inflammatory properties are now intensively researched as possible adjunctive or independent treatment options in IBD. Representatives of several different groups, including natural and chemical compounds will be characterized in this dissertation.

Multi-criteria Web Services Selection: Balancing the Quality of Design and Quality of Service

2022 ◽  
Vol 22 (1) ◽  
pp. 1-31
Author(s):  
Marwa Daaji ◽  
Ali Ouni ◽  
Mohamed Mohsen Gammoudi ◽  
Salah Bouktif ◽  
Mohamed Wiem Mkaouer
Keyword(s):  
Quality Of Service ◽  
Web Services ◽  
Web Service ◽  
State Of The Art ◽  
Service Selection ◽  
Service Design ◽  
Design Quality ◽  
Trade Off ◽  
Selection Approach

Web service composition allows developers to create applications via reusing available services that are interoperable to each other. The process of selecting relevant Web services for a composite service satisfying the developer requirements is commonly acknowledged to be hard and challenging, especially with the exponentially increasing number of available Web services on the Internet. The majority of existing approaches on Web Services Selection are merely based on the Quality of Service (QoS) as a basic criterion to guide the selection process. However, existing approaches tend to ignore the service design quality, which plays a crucial role in discovering, understanding, and reusing service functionalities. Indeed, poorly designed Web service interfaces result in service anti-patterns, which are symptoms of bad design and implementation practices. The existence of anti-pattern instances in Web service interfaces typically complicates their reuse in real-world service-based systems and may lead to several maintenance and evolution problems. To address this issue, we introduce a new approach based on the Multi-Objective and Optimization on the basis of Ratio Analysis method (MOORA) as a multi-criteria decision making (MCDM) method to select Web services based on a combination of their (1) QoS attributes and (2) QoS design. The proposed approach aims to help developers to maintain the soundness and quality of their service composite development processes. We conduct a quantitative and qualitative empirical study to evaluate our approach on a Quality of Web Service dataset. We compare our MOORA-based approach against four commonly used MCDM methods as well as a recent state-of-the-art Web service selection approach. The obtained results show that our approach outperforms state-of-the-art approaches by significantly improving the service selection quality of top- k selected services while providing the best trade-off between both service design quality and desired QoS values. Furthermore, we conducted a qualitative evaluation with developers. The obtained results provide evidence that our approach generates a good trade-off for what developers need regarding both QoS and quality of design. Our selection approach was evaluated as “relevant” from developers point of view, in improving the service selection task with an average score of 3.93, compared to an average of 2.62 for the traditional QoS-based approach.

scholarly journals Bone structural similarity score: a multiparametric tool to match properties of biomimetic bone substitutes with their target tissues

2016 ◽  
Vol 14 (3) ◽  
pp. 0-0 ◽  
Author(s):  
Giuseppe Falvo D’Urso Labate ◽  
Francesco Baino ◽  
Mara Terzini ◽  
Alberto Audenino ◽  
Chiara Vitale-Brovarone ◽  
...  
Keyword(s):  
Structural Similarity ◽  
Bone Substitutes ◽  
Similarity Score

scholarly journals ChemBioServer 2.0: an advanced web server for filtering, clustering and networking of chemical compounds facilitating both drug discovery and repurposing

2020 ◽  
Vol 36 (8) ◽  
pp. 2602-2604 ◽  
Author(s):  
Evangelos Karatzas ◽  
Juan Eiros Zamora ◽  
Emmanouil Athanasiadis ◽  
Dimitris Dellis ◽  
Zoe Cournia ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Perfect Match ◽  
Web Server ◽  
Drug Repurposing ◽  
Chemical Compounds ◽  
Structural Similarity ◽  
Substructure Search ◽  
Similarity Network ◽  
Compound Libraries ◽  
Network Analysis Metrics

Abstract Summary ChemBioServer 2.0 is the advanced sequel of a web server for filtering, clustering and networking of chemical compound libraries facilitating both drug discovery and repurposing. It provides researchers the ability to (i) browse and visualize compounds along with their physicochemical and toxicity properties, (ii) perform property-based filtering of compounds, (iii) explore compound libraries for lead optimization based on perfect match substructure search, (iv) re-rank virtual screening results to achieve selectivity for a protein of interest against different protein members of the same family, selecting only those compounds that score high for the protein of interest, (v) perform clustering among the compounds based on their physicochemical properties providing representative compounds for each cluster, (vi) construct and visualize a structural similarity network of compounds providing a set of network analysis metrics, (vii) combine a given set of compounds with a reference set of compounds into a single structural similarity network providing the opportunity to infer drug repurposing due to transitivity, (viii) remove compounds from a network based on their similarity with unwanted substances (e.g. failed drugs) and (ix) build custom compound mining pipelines. Availability and implementation http://chembioserver.vi-seem.eu.

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