Molecular docking and dynamic approach to virtual screen inhibitors against Esbp of Candidatus Liberibacter asiaticus

Saini, Gunjan; Dalal, Vikram; Savita, Brajesh Kumar; Sharma, Nidhi; Kumar, Pravindra; Sharma, Ashwani

doi:10.1016/j.jmgm.2019.08.012

Cited by 36 publications

(20 citation statements)

References 51 publications

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“…Molecular dynamics simulations results confirm that binding of PEP to ACE results in formations of stable ACE-PEP complex. Several molecular docking and simulation studies were used to predict the efficiency of binding of the ligand with macromolecules [30][31][32][33][34][35] . The ACE inhibitors such as captopril, lisinopril, enalapril, ramipril and perindopril have shown common side effects such as headache, dizziness, cough, low blood pressure, hypotension, nausea, and angioedema [36][37][38] .…”

Section: Discussionmentioning

confidence: 99%

Structural characterization and in-silico analysis of Momordica charantia 7S globulin for stability and ACE inhibition

Kesari

Pratap

Dhankhar

et al. 2020

Sci Rep

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Momordica charantia (Mc) seeds are widely used edible crop with high nutritional quality. The food and pharmaceutical industries use it as a natural anti-oxygenic agent. Herein, a ~52 kDa protein, which is a major part of seed proteome has been purified, biochemically characterized and structure has been determined. MALDI-ESI-MS identified peptide fragments and contig-deduced sequence suggested the protein to be homologous to 7S globulins. The crystal structure shows that protein has a bicupin fold similar to 7S globulins and the electron density for a copper and acetate ligand were observed in the C-terminal barrel domain. In silico study reveals that a tripeptide (VFK) from Mc7S possess a higher binding affinity for angiotensin converting enzyme (ACE) than already reported drug Lisinopril (LPR). The protein is a glycoprotein and highly stable under varying thermal and pH conditions due to its secondary structures. The DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay showed the protein to have an anti-oxygenic nature and can aid in scavenging free radical from sample. The protein can assist to enhance the nutritional and functional value of food by acting as a food antioxidant. Further, characterization of Mc7S required which might add in importance of Mc7S as antioxidant, anti-diabetic and anti-hypertensive. Momordica charantia (Mc) commonly known as bitter melon or bitter gourd is a member of Cucurbitaceae family, which grows in tropical and subtropical areas. The plant is known for centuries in Ayurveda for its anti-bacterial, anti-fungal, anti-viral, anti-parasitic, hypoglycemic, anti-fertility, anti-tumorous, and anti-carcinogenic properties 1-5. It is preferred as a medication for a broad range of health applications, including the treatment of dysmenorrhea, eczema, emmenagogue, galactagogue, gout, jaundice, kidney (stone), leprosy, leucorrhea, piles, pneumonia, psoriasis, rheumatism, scabies, T2DM (type 2 diabetes mellitus), obesity, hypertension, bacterial and viral infections, cancer, and even AIDS 1-5. It contains biologically active molecules including proteins, triterpenes, saponins, steroids, flavonoids, alkaloids, and acids 6. Each part of plant i.e. seeds, roots, leaves and especially unripe fruits has its pharmacological properties 4. The juice is used to cure a large number of conditions such as for articular pain relief and chronic fever in jaundice, liver disease, and digestive system diseases because of laxative, diuretic, and anti-helminthic effects. In the case of chronic skin diseases, it is applied locally to treat boils, burns, and rash. Moreover, components of Mc plant i.e. unripe fruit, seeds and aerial parts are largely known for its anti-diabetic properties due to the presence of insulin-mimetic in the seeds 7,8. The aqueous seed extract of Mc also scavenges the free radicals for protection against lipid peroxidation thereby reducing the risk of diabetic complications 9. The strong anti-oxygenic activity may be due to the presence of phenolic compounds and saponins 10. The globula...

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Section: Discussionmentioning

confidence: 99%

Structural characterization and in-silico analysis of Momordica charantia 7S globulin for stability and ACE inhibition

Kesari

Pratap

Dhankhar

et al. 2020

Sci Rep

Self Cite

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“…The topology of ligands (GMP, ZINC000257324845, ZINC000005169973 and ZINC000009913056) were predicted by PRODRG webserver, as done by , Sch€ uttelkopf and Van Aalten (2004). The partial atomic charges for ligands were computed by density functional theory (DFT) analysis using Lee-Yang-Parr correlation functional (B3LYP) method with a 6-311 G (d,p) basis set in Gaussian 16, as done by Frisch et al (2016), Jain et al (2004), Lee et al (1988), Saini et al (2019), Schlegel (1982). The protein-ligand complexes were solvated using a simple point charge (SPC) water model in a triclinic box of volume (234.61 nm 3 ) with a minimum distance of 1.0 nm between atoms of protein and edge of the box.…”

Section: Molecular Dynamics and Mmpbsamentioning

confidence: 99%

Computational guided identification of novel potent inhibitors of N-terminal domain of nucleocapsid protein of severe acute respiratory syndrome coronavirus 2

Dhankhar

Dalal

Singh

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The Coronavirus Disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 is an exceptionally contagious disease that leads to global epidemics with elevated mortality and morbidity. There are currently no efficacious drugs targeting coronavirus disease 2019, therefore, it is an urgent requirement for the development of drugs to control this emerging disease. Owing to the importance of nucleocapsid protein, the present study focuses on targeting the N-terminal domain of nucleocapsid protein from severe acute respiratory syndrome coronavirus 2 to identify the potential compounds by computational approaches such as pharmacophore modeling, virtual screening, docking and molecular dynamics. We found three molecules (ZINC000257324845, ZINC000005169973 and ZINC000009913056), which adopted a similar conformation as guanosine monophosphate (GMP) within the N-terminal domain active site and exhibiting high binding affinity (>À8.0 kcalmol À1). All the identified compounds were stabilized by hydrogen bonding with Arg107, Tyr111 and Arg149 of Nterminal domain. Additionally, the aromatic ring of lead molecules formed p interactions with Tyr109 of N-terminal domain. Molecular dynamics and Molecular mechanic/Poisson-Boltzmann surface area results revealed that N-terminal domainligand(s) complexes are less dynamic and more stable than N-terminal domain-GMP complex. As the identified compounds share the same corresponding pharmacophore properties, therefore, the present results may serve as a potential lead for the development of inhibitors against severe acute respiratory syndrome coronavirus 2.

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“…The final hits from pharmacophore screening were used for virtual screening using the crystal structure of NTD-N-protein. Virtual screening is a powerful technique for identifying the potential lead compounds in drug discovery (68)(69)(70)(71). Total 50 molecules bound at the active site of NTD and having higher binding energy than GMP were used for further study.…”

Section: Discussionmentioning

confidence: 99%

Computational Guided Identification of Novel Potent Inhibitors of NTD-N-Protein of SARS-CoV-2

Dhankhar¹,

Dalal²,

Singh³

et al. 2020

Preprint

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The Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus has raised severe health problems in china and across the world as well. CoVs encode the nucleocapsid protein (N-protein), an essential RNA-binding protein that performs different roles throughout the virus replication cycle and forms the ribonucleoprotein complex with viral RNA using the N-terminal domain (NTD) of N-protein. Recent studies have shown that NTD-N-protein is a legitimate target for the development of antiviral drugs against human CoVs. Owing to the importance of NTD, the present study focuses on targeting the NTD-N-protein from SARS-CoV-2 to identify the potential compounds. The pharmacophore model has been developed based on the guanosine monophosphate (GMP), a RNA substrate and further pharmacophore-based virtual screening was performed against ZINC database. The screened compounds were filtered by analysing the in silico ADMET properties and drug-like properties. The pharmacokinetically screened compounds (ZINC000257324845, ZINC000005169973, and ZINC000009913056) were further scrutinized through computational approaches including molecular docking and molecular dynamics simulations and revealed that these compounds exhibited good binding affinity as compared to GMP and provide stability to their respective complex with the NTD. Our findings could disrupt the binding of viral RNA to NTD, which may inhibit the essential functions of NTD. These findings may further provide an impetus to develop the novel and potential inhibitor against SARS-CoV-2.

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Molecular docking and dynamic approach to virtual screen inhibitors against Esbp of Candidatus Liberibacter asiaticus

Cited by 36 publications

References 51 publications

Structural characterization and in-silico analysis of Momordica charantia 7S globulin for stability and ACE inhibition

Structural characterization and in-silico analysis of Momordica charantia 7S globulin for stability and ACE inhibition

Computational guided identification of novel potent inhibitors of N-terminal domain of nucleocapsid protein of severe acute respiratory syndrome coronavirus 2

Computational Guided Identification of Novel Potent Inhibitors of NTD-N-Protein of SARS-CoV-2

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