scholarly journals In silico virtual screening approaches for anti-viral drug discovery

2012 ◽  
Vol 9 (3) ◽  
pp. e219-e225 ◽  
Author(s):  
Manuela S. Murgueitio ◽  
Marcel Bermudez ◽  
Jérémie Mortier ◽  
Gerhard Wolber
Keyword(s):  
Drug Discovery ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Approaches

Discovery of New AKT1 Inhibitors by Combination of In silico Structure Based Virtual Screening Approaches and Biological Evaluations

2019 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
suman sirimulla
Keyword(s):  
Virtual Screening ◽  
Success Rate ◽  
Protein Interactions ◽  
In Silico ◽  
Biological Data ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Screening Protocol ◽  
Screening Approaches

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

scholarly journals A Free Web-Based Protocol to Assist Structure-Based Virtual Screening Experiments

2019 ◽  
Vol 20 (18) ◽  
pp. 4648 ◽  
Author(s):  
Nathalie Lagarde ◽  
Elodie Goldwaser ◽  
Tania Pencheva ◽  
Dessislava Jereva ◽  
Ilza Pajeva ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Virtual Screening ◽  
Web Service ◽  
Molecular Mechanics ◽  
In Silico ◽  
Chemical Biology ◽  
In Silico Screening ◽  
Web Based ◽  
Screening Experiments ◽  
The Web

Chemical biology and drug discovery are complex and costly processes. In silico screening approaches play a key role in the identification and optimization of original bioactive molecules and increase the performance of modern chemical biology and drug discovery endeavors. Here, we describe a free web-based protocol dedicated to small-molecule virtual screening that includes three major steps: ADME-Tox filtering (via the web service FAF-Drugs4), docking-based virtual screening (via the web service MTiOpenScreen), and molecular mechanics optimization (via the web service AMMOS2 [Automatic Molecular Mechanics Optimization for in silico Screening]). The online tools FAF-Drugs4, MTiOpenScreen, and AMMOS2 are implemented in the freely accessible RPBS (Ressource Parisienne en Bioinformatique Structurale) platform. The proposed protocol allows users to screen thousands of small molecules and to download the top 1500 docked molecules that can be further processed online. Users can then decide to purchase a small list of compounds for in vitro validation. To demonstrate the potential of this online-based protocol, we performed virtual screening experiments of 4574 approved drugs against three cancer targets. The results were analyzed in the light of published drugs that have already been repositioned on these targets. We show that our protocol is able to identify active drugs within the top-ranked compounds. The web-based protocol is user-friendly and can successfully guide the identification of new promising molecules for chemical biology and drug discovery purposes.

Discovery of new AKT1 inhibitors by combination of in silico structure based virtual screening approaches and biological evaluations

2020 ◽  
Vol 39 (1) ◽  
pp. 368-377 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
Ashish Tyagi ◽  
Chendil Damodaran ◽  
...  
Keyword(s):  
Virtual Screening ◽  
In Silico ◽  
Screening Approaches

Discovery of New AKT1 Inhibitors by Combination of In silico Structure Based Virtual Screening Approaches and Biological Evaluations

2019 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
suman sirimulla
Keyword(s):  
Virtual Screening ◽  
Success Rate ◽  
Protein Interactions ◽  
In Silico ◽  
Biological Data ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Screening Protocol ◽  
Screening Approaches

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

An in silico structure-based approach to anti-infective drug discovery

Parasitology ◽  
2013 ◽  
Vol 141 (1) ◽  
pp. 17-27 ◽  
Author(s):  
FRASER CUNNINGHAM ◽  
MARTIN J. McPHILLIE ◽  
A. PETER JOHNSON ◽  
COLIN W. G. FISHWICK
Keyword(s):  
Drug Discovery ◽  
In Silico ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Enzyme Inhibitors ◽  
Cell Activity ◽  
Structure Based Drug Design ◽  
Lead Compounds ◽  
Target Mode ◽  
Screening Approaches

SUMMARYIn light of the low success rate of target-based genomics and HTS (High Throughput Screening) approaches in anti-infective drug discovery, in silico structure-based drug design (SBDD) is becoming increasingly prominent at the forefront of drug discovery. In silico SBDD can be used to identify novel enzyme inhibitors rapidly, where the strength of this approach lies with its ability to model and predict the outcome of protein-ligand binding. Over the past 10 years, our group have applied this approach to a diverse number of anti-infective drug targets ranging from bacterial D-ala-D-ala ligase to Plasmodium falciparum DHODH. Our search for new inhibitors has produced lead compounds with both enzyme and whole-cell activity with established on-target mode of action. This has been achieved with greater speed and efficiency compared with the more traditional HTS initiatives and at significantly reduced cost and manpower.

scholarly journals In-silico protein-ligand docking studies against the estrogen protein of breast cancer using pharmacophore based virtual screening approaches

2021 ◽  
Vol 28 (1) ◽  
pp. 400-407
Author(s):  
Jesudass Joseph Sahayarayan ◽  
Kulanthaivel Soundar Rajan ◽  
Ramasamy Vidhyavathi ◽  
Mutharasappan Nachiappan ◽  
Dhamodharan Prabhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Virtual Screening ◽  
In Silico ◽  
Docking Studies ◽  
Ligand Docking ◽  
Screening Approaches

scholarly journals Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4723 ◽  
Author(s):  
Javier Vázquez ◽  
Manel López ◽  
Enric Gibert ◽  
Enric Herrero ◽  
F. Javier Luque
Keyword(s):  
Drug Discovery ◽  
Virtual Screening ◽  
Molecular Similarity ◽  
Computational Framework ◽  
Widespread Application ◽  
Virtual Libraries ◽  
Available Information ◽  
Novel Drug ◽  
Discovery Pipeline ◽  
Screening Approaches

Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued efforts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature.

scholarly journals Paradoxical Pro-angiogenic Effect of Low-Dose Ellipticine Identified by In Silico Drug Repurposing

2021 ◽  
Vol 22 (16) ◽  
pp. 9067
Author(s):  
Jisu Oh ◽  
Hyeon Hae Lee ◽  
Yunhui Jeong ◽  
Siyeong Yoon ◽  
Hyun-Ju An ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Virtual Screening ◽  
In Silico ◽  
Glycogen Synthase ◽  
Docking Simulation ◽  
Drug Repurposing ◽  
Structural Similarity ◽  
Gene Expression Omnibus ◽  
Screening Tools ◽  
Drug Candidate

Inadequate vessel maintenance or growth causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative disorders. Therefore, developing an effective strategy to salvage ischemic tissues using a novel compound is urgent. Drug repurposing has become a widely used method that can make drug discovery more efficient and less expensive. Additionally, computational virtual screening tools make drug discovery faster and more accurate. This study found a novel drug candidate for pro-angiogenesis by in silico virtual screening. Using Gene Expression Omnibus (GEO) microarray datasets related to angiogenesis studies, differentially expressed genes were identified and characteristic direction signatures extracted from GEO2EnrichR were used as input data on L1000CDS2 to screen pro-angiogenic molecules. After a thorough review of the candidates, a list of compounds structurally similar to TWS-119 was generated using ChemMine Tools and its clustering toolbox. ChemMine Tools and ChemminR structural similarity search tools for small-molecule analysis and clustering were used for second screening. A molecular docking simulation was conducted using AutoDock v.4 to evaluate the physicochemical effect of secondary-screened chemicals. A cell viability or toxicity test was performed to determine the proper dose of the final candidate, ellipticine. As a result, we found ellipticine, which has pro-angiogenic effects, using virtual computational methods. The noncytotoxic concentration of ellipticine was 156.25 nM. The phosphorylation of glycogen synthase kinase-3β was decreased, whereas the β-catenin expression was increased in human endothelial cells treated with ellipticine. We concluded that ellipticine at sublethal dosage could be successfully repositioned as a pro-angiogenic substance by in silico virtual screening.

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