scholarly journals Identification of DNA gyrase Subunit a Mutations Associated with Ciprofloxacin Resistance in Staphylococcus aureus Isolated from Nasal Infection in Kurdistan-Iran

2017 ◽  
Vol 7 (1) ◽  
pp. 186
Author(s):  
Roya Darbani ◽  
Chiako Farshadfar ◽  
Somayeh Tavana ◽  
Hamidreza Saljoughi ◽  
Sheida Sadat Zonouri
Keyword(s):  
Staphylococcus Aureus ◽  
Free Energy ◽  
Molecular Docking ◽  
Dna Gyrase ◽  
Amino Acid Sequences ◽  
Nucleotide Sequencing ◽  
Molegro Virtual Docker ◽  
Fluoroquinolone Antibiotics ◽  
Ciprofloxacin Resistance ◽  
Free Energy Of Binding

Fluoroquinolone antibiotics such as ciprofloxacin are useful drugs against infections caused by Staphylococcus aureus and mutations in DNA gyrase which control bacterial DNA topology, can be one of the reason of occurrence resistance to this class of antibiotics. Therefore finding new mutations and study of the quinolone interaction with mutated GyrA can provide important issues for explanation resistance. In this study 5 ciprofloxacin resistance Staphylococcus aureus isolated among 50 collected S.aureus strains. By PCR testing, gyrA genes in resistance strains was amplified and nucleotide sequencing was done. Nucleotide sequences translate to amino acid sequences then by blastp homology between each GyrA mutant and reference GyrA were compared and mutations were recognized, at last molecular docking were done for GyrA protein and ciprofloxacin, based on free energy of binding decide if the mutations are responsible of resistance or not. The results show glutamic acid and threonine adjacent to each other in common positions 21-22, 32-33, 65-66, 84-85, 101-102, 106-107, 128-129 and 138-139 in all 5 strains were inserted . In order to finding association between mutations and ciprofloxacin resistance molecular docking by Molegro Virtual Docker 5.5 was done. Free energy of binding between reference GyrA- ciprofloxacin and mutant GyrA- ciprofloxacin were -92.3477 and -73.1642 respectively. We conclude different mutations can be affected structure of GyrA and make ciprofloxacin resistance. Finding these kinds of mutations are important and preventing them is indispensable.

scholarly journals Identification of Ciprofloxacin-ResistantCampylobacter jejuni by Use of a Fluorogenic PCR Assay

2000 ◽  
Vol 38 (11) ◽  
pp. 3971-3978 ◽  
Author(s):  
David L. Wilson ◽  
Sheila R. Abner ◽  
Thomas C. Newman ◽  
Linda S. Mansfield ◽  
John E. Linz
Keyword(s):  
Antimicrobial Agents ◽  
Sequence Data ◽  
Dna Gyrase ◽  
Species Level ◽  
Primary Target ◽  
Pcr Assay ◽  
Nucleotide Sequence Data ◽  
Rapid Pcr ◽  
Fluoroquinolone Antibiotics ◽  
Ciprofloxacin Resistance

Fluoroquinolones are one class of antimicrobial agents commonly used to treat severe Campylobacter jejuni infection.C. jejuni strains resistant to high levels of the fluoroquinolone ciprofloxacin (MIC ≥16 μg/ml) have been predominantly characterized with a C→T transition in codon 86 ofgyrA. The gyrA gene encodes one subunit of DNA gyrase, which is a primary target for fluoroquinolone antibiotics. This study establishes a rapid PCR-based TaqMan method for identifying ciprofloxacin-resistant C. jejuni strains that carry the C→T transition in codon 86 of gyrA. The assay uses real-time detection, eliminating the need for gel electrophoresis. Optimization of the assay parameters using purified Campylobacter DNA resulted in the ability to detect femtogram levels of DNA. The method should be useful for monitoring the development of ciprofloxacin resistance in C. jejuni. Compiled nucleotide sequence data on the quinolone resistance-determining region of gyrA inCampylobacter indicate that sequence comparison of this region is a useful method for tentative identification ofCampylobacter isolates at the species level.

scholarly journals A Molecular Docking Study of N-Ferrocenylmethylnitroanilines as Potential Anticancer Drugs

2016 ◽  
Vol 2 ◽  
pp. 5-12 ◽  
Author(s):  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
Protein Structure ◽  
Dna Gyrase ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Gyrase A

In the present study, the interaction of the protein structure of Escherichia coli DNA Gyrase-A (EcGyr-A) extracted from protein data bank (PDB Code: 1AB4) with ligands N-ferrocenylmethyl-2-nitroaniline (2FMNA), N-ferrocenylmethyl-3-nitroaniline (3FMNA) and N-ferrocenylmethyl-4-nitroaniline (4FMNA) were investigated by performing docking studies using the Molegro Virtual Docker (MVD) software. The results obtained showed that the best poses which is derived from MolDock score for Escherichia coli DNA Gyrase-A were respectively equal to-92.0111, -96.0866 and-95.6808 with reranking score equal to-40.9575, -73.4476 and-73.6423. Calculations revealed that 3FMNA react strongly with EcGyr-A followed by 4-FMNA and 2-FMNA.

scholarly journals Molecular Docking, ADME Analysis, and Estimation of MM/GBSA Binding-Free Energies of Coumarin Derivatives as Potential Inhibitors of SARS CoV-2 Receptors

2020 ◽  
Author(s):  
Akhilesh Kumar Maurya ◽  
Nidhi Mishra
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Severe Acute Respiratory Syndrome ◽  
Specific Drug ◽  
Coumarin Derivatives ◽  
Free Energies ◽  
Potential Inhibitors ◽  
Stimulatory Factor ◽  
Free Energy Of Binding ◽  
Binding Free Energies

Abstract Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Currently, there is no specific drug for the therapy of COVID-19. In the present study, in silico study have been done to find out possible inhibitors of SARS CoV-2. Coumarin derivatives with 2755 compounds were virtually screen against methyltransferase-stimulatory factor complex of NSP16 and NSP10, NSP15 Endoribonuclease, ADP ribose phosphatase (ADRP)of NSP3 and protease enzymes of SARS CoV-2. Docked top five compounds showed good docking scores and free energy of binding with the respective receptors. ADME/T analysis of docked compound shows the docked ligands are showing drug-likeness properties.

Novel Benzotriazole acetamide derivatives as Benzo-Fused Five-Membered Nitrogen-Containing Heterocycle- Insilico Screening, Molecular Docking, and Synthesis

2021 ◽  
Vol 18 ◽  
Author(s):  
Patil Tejaswini D. ◽  
Amrutkar Sunil V.
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Docking ◽  
Active Site ◽  
Antibacterial Agent ◽  
Antibacterial Properties ◽  
Dna Gyrase ◽  
Antibacterial Drug ◽  
E Coli ◽  
Fast Development ◽  
Subunit B

Background: DNA gyrase subunit B (1KZN) is an attractive target for antibacterial drug development because of its role in DNA replication. The fast development of antimicrobial medication resistance necessitates the quick discovery of new antimicrobial medicines. Objective: The goal of this research is to design, synthesize, and discover benzo-fused five-membered nitrogen-containing heterocycles that bind to DNA gyrase subunit B via molecular docking (1KZN). Methods: Based on literature research, 2-(1H-1,2,3-Benzotriazol-1-yl)-N-substituted acetamide was synthesized using an efficient method. All synthesized compounds were evaluated for antibacterial activity against three distinct organisms: E. coli, Pseudomonas aeruginosa, Staphylococcus aureus. In a docking investigation, the chemical interacts with the active site of DNA gyrase subunit B (1KZN), indicating that it might have antibacterial action. Conclusion: According to the findings of this research, the compounds 3d and 3f show antibacterial properties. For Staphylococcus aureus, 3c has the potential to be an antibacterial agent.

Incorporating replacement free energy of binding-site waters in molecular docking

2014 ◽  
Vol 82 (9) ◽  
pp. 1765-1776 ◽  
Author(s):  
Hanzi Sun ◽  
Lifeng Zhao ◽  
Shiming Peng ◽  
Niu Huang
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Binding Site ◽  
Free Energy Of Binding

scholarly journals Molecular docking approach to elucidate metabolic detoxification pathway of polycyclic aromatic hydrocarbons

2021 ◽  
pp. 150-161
Author(s):  
Mohammad Kalim Ahmad Khan ◽  
Salman Akhtar ◽  
Fahad Al-Khodairy
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Aromatic Hydrocarbons ◽  
Glutathione S Transferase ◽  
Drug Discovery And Development ◽  
Docking Approach ◽  
Polycyclic Aromatic ◽  
Metabolic Detoxification ◽  
Free Energy Of Binding ◽  
Detoxification Pathway

This study assessed the molecular interactions of (±)-anti-and-syn- dibenzo[a,l]pyrene-11,12-diol-13,14-epoxide (DBPDE), 7,12- dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide (DMBADE), N2- hydroxylated-PhIP(N2-OH-PhIP), (±)-anti-and-syn-benzo[a]pyrene-7,8-diol- 9,10-epoxide (BPDE) with various Glutathione S-transferase (GST) and N- acetyltransferase (NAT) isozymes. Our in-silico data revealed that GSTP1 (- 8.83 kcal/mol), showing more plausible binding as compared to GSTM1 (-8.74 kcal/mol) and GSTA1 (ΔG: -8.03 kcal/mol) against (-)-anti-DBPDE and (+)- syn-DBPDE. We also investigated the involvement of GST and NAT isozymes in the conjugation of DMBADE andN2-OH-PhIP as a control despite their preferred routes sulfonation and glucuronidation for detoxification. The findings exhibited feeble binding of different classes of GSTs with metabolites of DMBA and PhIP, as highlighted by their free energy of binding. The enzymatic activity of GSTM1 against the most potent diol-epoxide of benzo[a]pyrene (BP), (+)-anti-BPDE, and (+)-syn-BPDE followed by GSTP1 and GSTA1 has well documented. In addition, these findings provide new perspectives for most probable mechanistic details of the detoxification pathway of PAHs and xenobiotics useful in combination therapy for future ligand-based drug discovery and development.

scholarly journals ANTIBACTERIAL ACTIVITY OF AKAR KUNING (ARCANGELISIA FLAVA) SECONDARY METABOLITES: MOLECULAR DOCKING APPROACH

2018 ◽  
Vol 11 (11) ◽  
pp. 447 ◽  
Author(s):  
Mohammad Rizki Fadhil Pratama ◽  
Suratno S ◽  
Evi Mulyani
Keyword(s):  
Cell Wall ◽  
Free Energy ◽  
Molecular Docking ◽  
Secondary Metabolites ◽  
Acid Synthesis ◽  
Allosteric Site ◽  
Protein Nucleic Acid ◽  
Cell Wall Inhibition ◽  
Inhibitor Of Protein Synthesis ◽  
Free Energy Of Binding

Objectives: Akar kuning (Arcangelisia flava) was known to have various pharmacological activities including as antibacterial. Several Gram-positive and Gram-negative bacteria show response to akar kuning secondary metabolites, although the type of metabolites that inhibit the growth of each type of bacteria not yet known. This study aims to obtain the prediction of metabolites from akar kuning with the greatest antibacterial potential against various types of antibacterial receptors.Methods: Molecular docking was performed using Autodock Vina 1.1.2 on several secondary metabolites of akar kuning against active site of several antibacterial receptors that were known for many antibiotics including as cell wall, protein, nucleic acid synthesis inhibitors, and antimetabolites. The main parameter used was the free energy of binding as affinity marker.Results: The docking results show that among 11 metabolites studied, 6-hydroxyfibraurin, berberine, and fibleucin provided the lowest free energy of binding between 11 antibacterial receptors compared with natural substrates or inhibitors from each receptor. Interesting results show by berberine as inhibitor of protein synthesis with possibility of allosteric site discovery. Berberine also shows more than 75% similarity with natural substrate of cell wall inhibition receptor, indicating possible similar type of interaction.Conclusion: Overall, it seems that for the selected secondary metabolites of akar kuning, the main mechanism of action was the inhibition of protein and cell wall synthesis, which was shown by berberine.

scholarly journals Molecular docking study of sappan wood extract to inhibit PBP2A enzyme on methicillin-resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 30 (6) ◽  
Author(s):  
Marisca Evalina Gondokesumo ◽  
Ihsan Mulyadi Kurniawan
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Taste Disturbance ◽  
Methicillin Resistant ◽  
Molegro Virtual Docker ◽  
Important Interaction ◽  
Wood Extract

AbstractBackgroundPBP2a is a type of penicillin-binding proteins (PBPs) that cause resistivity in methicillin-resistant Staphylococcus aureus (MRSA) from β-lactam antibiotics. MRSA susceptible with cefttobiprole (fifth generation of cephalosporin as an anti-MRSA agent) which inhibits PBP2a and stops its growth. Contrary to its efficacy, ceftobiprole causes taste disturbance more than any other cephalosporins; furthermore, its mechanism is unknown. This study aims to explore an in silico study of a natural compound, which serves as a potential alternative to overcome MRSA with minimum adverse side effects.MethodsA molecular docking study was performed using Molegro Virtual Docker version 5.5. Brazilin and proto-sappanins A–E are phytochemical compounds contained in sappan wood extract and are docked into the binding site of PBP2a (Protein Data Bank: ID 4DKI).ResultsBrazilin and proto-sappanins A–E have some interaction with Ser 403 amino acid residue which is an important interaction to inhibit PBP2a protein. The result of the molecular docking study showed that the MolDock score of proto-sappanins D and E is lower than that of methicillin but higher than that of its native ligand (ceftobiprole).ConclusionsThe results of this study suggest that proto-sappanins D and E have an excellent potential activity as an alternative to ceftobiprole in limiting MRSA growth through PBP2A enzyme inhibition.

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