scholarly journals Homology Model and Docking-Based Virtual Screening for Ligands of the σ1 Receptor

2011 ◽  
Vol 2 (11) ◽  
pp. 834-839 ◽  
Author(s):  
Erik Laurini ◽  
Valentina Dal Col ◽  
Maria Grazia Mamolo ◽  
Daniele Zampieri ◽  
Paola Posocco ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Homology Model ◽  
Σ1 Receptor

Comprehensive in silico Study of GLUT10: Prediction of Possible Substrate Binding Sites and Interacting Molecules

2020 ◽  
Vol 21 (2) ◽  
pp. 117-130 ◽  
Author(s):  
Mohammad J. Hosen ◽  
Mahmudul Hasan ◽  
Sourav Chakraborty ◽  
Ruhshan A. Abir ◽  
Abdullah Zubaer ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Binding Site ◽  
Glucose Transporter ◽  
Substrate Binding ◽  
Mutation Screening ◽  
Homology Model ◽  
Connective Tissue Disorder ◽  
Crystallographic Structure ◽  
Substrate Binding Site

Objectives: The Arterial Tortuosity Syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and stenosis of the arteries with a propensity towards aneurysm formation and dissection. It is caused by mutations in the SLC2A10 gene that encodes the facilitative glucose transporter GLUT10. The molecules transported by and interacting with GLUT10 have still not been unambiguously identified. Hence, the study attempts to identify both the substrate binding site of GLUT10 and the molecules interacting with this site. Methods: As High-resolution X-ray crystallographic structure of GLUT10 was not available, 3D homology model of GLUT10 in open conformation was constructed. Further, molecular docking and bioinformatics investigation were employed. Results and Discussion: Blind docking of nine reported potential in vitro substrates with this 3D homology model revealed that substrate binding site is possibly made with PRO531, GLU507, GLU437, TRP432, ALA506, LEU519, LEU505, LEU433, GLN525, GLN510, LYS372, LYS373, SER520, SER124, SER533, SER504, SER436 amino acid residues. Virtual screening of all metabolites from the Human Serum Metabolome Database and muscle metabolites from Human Metabolite Database (HMDB) against the GLUT10 revealed possible substrates and interacting molecules for GLUT10, which were found to be involved directly or partially in ATS progression or different arterial disorders. Reported mutation screening revealed that a highly emergent point mutation (c. 1309G>A, p. Glu437Lys) is located in the predicted substrate binding site region. Conclusion: Virtual screening expands the possibility to explore more compounds that can interact with GLUT10 and may aid in understanding the mechanisms leading to ATS.

Identification of a Potential Inhibitor Targeting MurC Ligase of the Drug Resistant Pseudomonas aeruginosa Strain through Structure-Based Virtual Screening Approach and In Vitro Assay

2019 ◽  
Vol 20 (14) ◽  
pp. 1203-1212
Author(s):  
Abdelmonaem Messaoudi ◽  
Manel Zoghlami ◽  
Zarrin Basharat ◽  
Najla Sadfi-Zouaoui
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virtual Screening ◽  
Homology Model ◽  
Generation Cephalosporin ◽  
World Health ◽  
Resistant Bacteria ◽  
Antimicrobial Drugs ◽  
Vitro Assay ◽  
Priority List

Background & Objective: Pseudomonas aeruginosa shows resistance to a large number of antibiotics, including carbapenems and third generation cephalosporin. According to the World Health Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a good target for the discovery of novel antimicrobial drugs. Methods: Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target for the design of new classes of antimicrobial inhibitors in gram-negative bacteria. Results: In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally through inhibition assay. Conclusion: The presented results based on combined computational and in vitro analysis open up new horizons for the development of novel antimicrobials against this pathogen.

Virtual Screening of Inhibitors Against Spike Glycoprotein of SARS-CoV-2: A Drug Repurposing Approach

2020 ◽  
Author(s):  
Kanishka Senathilake ◽  
Sameera Samarakoon ◽  
Kamani Tennekoon
Keyword(s):  
Virtual Screening ◽  
Drug Repurposing ◽  
Homology Model ◽  
Respiratory Illness ◽  
Receptor Interaction ◽  
S Protein ◽  
Surface Receptors ◽  
High Affinity ◽  
Food Dye ◽  
Novel Coronavirus

The novel coronavirus (SARS-CoV-2) is a human pathogen recently emerged in China, causing a global pandemic of severe respiratory illness (COVID19). SARS-CoV-2 makes entry into human cells through its spike (S) protein that binds to cell surface receptors. Widespread of SARS-CoV-2 has been attributed to high affinity of S protein to its receptor. A homology model of the receptor binding domain of SARS-CoV-2 S protein (RBD) was built. RBD- receptor docking and published molecular dynamics data were used to map the key RBD-receptor interaction hotspot (RBDhp) on the RBD. Primary virtual screening was carried out against RBDhp using more than 3300 compounds approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Compounds that bind to hpRBD with a binding energy ≤ - 6.5 kcal/mol were subjected to secondary screening using a recently published cryo EM (2.9 Å) structure of RBD. A cardiac glycoside (dgitoxin), two anthracyclines (zorubicin and aclarubicin), a tetracycline derivative (rolitetracycline), a cephalosporin (cefoperazone) and a food dye (E-155) were predicted to be most potent inhibitors of RBD – receptor interaction. An anti-asthmatic drug (zafirlukast) and several other drugs (itrazol, fazadinium, troglitazone, gliquidone, Idarubicin, Oxacillin) were found to be high affinity binders that may have a potential to inhibit RBD – receptor interaction.

First Pharmacophore Model of CCR3 Receptor Antagonists and its Homology Model-Assisted, Stepwise Virtual Screening

2011 ◽  
Vol 77 (5) ◽  
pp. 373-387 ◽  
Author(s):  
Vaibhav Jain ◽  
Parameswaran Saravanan ◽  
Akanksha Arvind ◽  
Chethampadi Gopi Mohan
Keyword(s):  
Virtual Screening ◽  
Pharmacophore Model ◽  
Homology Model ◽  
Receptor Antagonists

IKKβ inhibitors identification part I: Homology model assisted structure based virtual screening

2009 ◽  
Vol 17 (7) ◽  
pp. 2759-2766 ◽  
Author(s):  
Shanthi Nagarajan ◽  
Munikumar reddy Doddareddy ◽  
Hyunah Choo ◽  
Yong Seo Cho ◽  
Kwang-Seok Oh ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Homology Model

Impact of Template Choice on Homology Model Efficiency in Virtual Screening

2014 ◽  
Vol 54 (6) ◽  
pp. 1661-1668 ◽  
Author(s):  
Krzysztof Rataj ◽  
Jagna Witek ◽  
Stefan Mordalski ◽  
Tomasz Kosciolek ◽  
Andrzej J. Bojarski
Keyword(s):  
Virtual Screening ◽  
Homology Model ◽  
Model Efficiency

scholarly journals Discovery of Amoebicidal Compounds by Combining Computational and Experimental Approaches

2020 ◽  
Author(s):  
Víctor Sebastián-Pérez ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
Angélica Domínguez-De Barros ◽  
Atteneri López-Arencibia ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Therapeutic Potential ◽  
Homology Model ◽  
Chemical Library ◽  
Granulomatous Amoebic Encephalitis ◽  
Screening Protocol ◽  
Recent Developments ◽  
Experimental Approaches ◽  
Lengthy Treatment

Pathogenic and opportunistic free-living amoebae such as Acanthamoeba spp. can cause keratitis (AK), which may ultimately lead to permanent visual impairment or blindness. Acanthamoeba can also cause a rare but usually fatal granulomatous amoebic encephalitis (GAE). Current therapeutic options for AK require a lengthy treatment with nonspecific drugs that often are associated with adverse effects. Recent developments in the field led us to target cAMP pathways, specifically phosphodiesterase. Guided by computational tools we targeted the Acanthamoeba phosphodiesterase, RegA. Computational studies led to the construction and validation of a homology model followed by a virtual screening protocol guided by induced-fit docking and chemical scaffold analysis using our MBC chemical library. Subsequently, 18 virtual screening hits were prioritized for further testing in vitro against A. castellanii, identifying amoebicidal hits containing piperidine and urea imidazole cores. Promising activities were confirmed in the resistant cyst form of the amoeba and in additional clinical Acanthamoeba strains, increasing their therapeutic potential. Mechanism of action studies revealed that these compounds produce apoptosis through ROS-mediated mitochondrial damage. These chemical families show promise for further optimization to produce effective anti-Acanthamoebal drugs.

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