Modeling studies of arginase from Helicobacter pylori divulge novel inhibitor-protein interactions

Gacche, Rajesh N.; Meshram, Rohan J.; Dawane, Ashwini A.; Kamble, Sonali S.; Shinde, Ganpat P.; Dhabadge, Vivek N.; Patil, Kapil

doi:10.15761/cpb.1000113

Cited by 3 publications

(2 citation statements)

References 48 publications

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“…In preparation for molecular docking, all the ligands were uploaded on the virtual screening software, PyRx (Python prescription) 0.8 version using the Open Babel plug-in tool [17] and converted from sdf to Protein Data Bank, Partial Charge, & Atom Type (pdbqt) format [18]. For stable conformation, the Universal Force Field (UFF) was used as the energy minimization parameter and conjugate gradient descent as the optimization algorithm.…”

Section: Molecular Docking and Virtual Screeningmentioning

confidence: 99%

In-silico Investigation of Potential Inhibitors of 11-β-Hydroxysteroid Dehydrogenase

Hassan,

Sadiya,

Jafaru

et al. 2023

AJBGMB

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Diabetes mellitus is a chronic disease plagued with insufficient insulin production or insulin resistance. New targets and disease pathways are emerging and one such is the 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyses the intracellular conversion of inert cortisone to physiologically active cortisol, functioning to enhance local cortisol action beyond what would be predicted based on simple plasma exposures. This study aimed at exploring the anti-diabetic potential of the bioactive compounds found in Carica papaya. In this study, 59 natural compounds were obtained from literature are used for molecular docking simulations against the 11β-HSD1 receptor target using the Python Prescription (PyRx) 0.8 software. An arbitrary docking score ≤ -8.0 kcal/mol was chosen as the cut-off value. Further screening for drug-likeness, Absorption Distribution Metabolism Excretion and Toxicity (ADMET) properties, Pan Assay Interference Compounds (PAINS), and bioactivity were performed. The compounds were compared to the 11β-HSD1 inhibitor, MK-0916 which was the reference compound and docked against the target with a binding affinity of -8.8 kcal/mol. After docking, 11 compounds emerged with docking of ≤-8.0 kcal/mol, the highest at -8.1 kcal/mol and lowest at -10.7 kcal/mol. The compounds were further screened using Ghose and Verber rule resulting in four compounds i.e. Ibogamine, Clausamine G, Dasycarpidan-1-methanol, acetate (ester) and Phenol-2-methyl-5- (1,2,2- trimethylcyclopentyl). Pharmacokinetic screening (ADMET and bioactivity) was carried out on the four compounds and it was discovered that they have a level of potency but Ibogamine has higher potency of exerting inhibitory function on 11β-HSD1 compared to the control.

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Section: Molecular Docking and Virtual Screeningmentioning

confidence: 99%

In-silico Investigation of Potential Inhibitors of 11-β-Hydroxysteroid Dehydrogenase

Hassan,

Sadiya,

Jafaru

et al. 2023

AJBGMB

View full text Add to dashboard Cite

show abstract

“…In preparation for molecular docking, all the ligands were uploaded on the virtual screening software, PyRx (Python prescription) 0.8 version using the Open Babel plug-in tool [24] and converted from sdf to Protein Data Bank, Partial Charge, & Atom Type (pdbqt) format [25]. For stable conformation, the Universal Force Field (UFF) was used as the energy minimization parameter and conjugate gradient descent as the optimization algorithm.…”

Section: Molecular Docking and Virtual Screeningmentioning

confidence: 99%

In Silico Identification of the Potential Natural Inhibitors of SARS-CoV-2 Guanine-N7 Methyltransferase.

Rowaiye¹,

Onuh²,

Oladimeji-Salami³

et al. 2020

Preprint

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The outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 has triggered intense scientific research into the possible therapeutic strategies that can combat the ravaging disease. One of such strategies is the inhibition of an important enzyme that affects an important physiological process of the virus. The enzyme, Guanine 7 Methyltransferase is responsible for the capping of the SARS-CoV-2 mRNA to conceal it from the host’s cellular defense. The study aims at computationally identifying the potential natural inhibitors of the SARS-CoV-2 GuanineN7 methyltransferase binding at the active site (Pocket 41). A library of small molecules was obtained from edible African plants and were molecularly docked against the SARS-CoV-2 Guanine-N7 methyltransferase (QHD43415_13. pdb) using the Pyrx software. Sinefungin, an approved antiviral drug which had a binding score of -7.6 kcal/ mol with the target was chosen as a standard. Using the molecular descriptors of the compounds, a virtual screening for oral availability was performed using the Pubchem and SWISSADME web tools. The online servers PKCSM and Molinspiration were used for further screening for pharmacokinetic properties and bioactivity respectively. The molecular dynamic simulation and analyses of the Apo and Holo proteins was performed using the GROMACS software on the Galaxy webserver. The lead compounds are Crinamidine, Marmesin and Sinensetin which are obtained from waterleaf, mango, and orange plants respectively. All the lead compounds performed better than the standard. Crinamidine is predicted to show the greatest inhibitory activity. Further tests are required to further investigate the inhibitory activities of the lead compounds.

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In silico design and in vitro assessment of anti-Helicobacter pylori compounds as potential small-molecule arginase inhibitors

et al. 2022

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Modeling studies of arginase from Helicobacter pylori divulge novel inhibitor-protein interactions

Cited by 3 publications

References 48 publications

In-silico Investigation of Potential Inhibitors of 11-β-Hydroxysteroid Dehydrogenase

In-silico Investigation of Potential Inhibitors of 11-β-Hydroxysteroid Dehydrogenase

In Silico Identification of the Potential Natural Inhibitors of SARS-CoV-2 Guanine-N7 Methyltransferase.

In silico design and in vitro assessment of anti-Helicobacter pylori compounds as potential small-molecule arginase inhibitors

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