Molecular modelling on SARS-CoV-2 papain-like protease: an integrated study with homology modelling, molecular docking, and molecular dynamics simulations

Arwansyah, Arwansyah; Arif, Abdur Rahman; Ramli, Irwan; Kurniawan, Isman; Sukarti, Sukarti; Alam, Masqudul; Illing, Ilmiati; Lewa, A Farid; Manguntungi, B

doi:10.1080/1062936x.2021.1960601

Cited by 12 publications

(7 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From our docking simulation, we suggested that three ligands, i.e., diposphoryl lipid A, FC-core lipid A, and Kdo2 lipid A, can be activators of the factor C protein by binding to the region of the receptor to form a ligandreceptor complex. Therefore, three structures (complexes 2, 3, and 4) were selected for further analysis [45].…”

Section: Discussionmentioning

confidence: 99%

“…From this figure, all complexes involved fluctuations during the simulation. The fluctuation along simulation can be influenced by atomics interactions in the system via electrostatic interaction and hydrogen and hydrophobic interactions which involve structural rearrangement at the protein and ligand molecule interface [22,45]. Moreover, the factor C protein has a large structure (1019 amino acids) with several domains placing different regions which make the protein structure tend to fluctuate along the MD simulation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization, protein modeling, and molecular docking of factor C from Indonesian horseshoe crab (Tachypleus gigas)

Mustopa

Izaki

Suharsono

et al. 2023

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

Background Horseshoe crab (Tachypleus gigas) amebocytes are useful biomedical components for endotoxin detection, and their growing needs for biomedical purposes cause the horseshoe crab population to decline. Factor C synthesis via genetic engineering offers a solution to replace natural horseshoe crab’s factor C and prevent its excessive harvest from nature. In response to these concerns, this study aimed to characterize the amebocyte lysates and factor C protein modeling of T. gigas originated from Banyuasin South Sumatra Estuary. Methods and results Sampling of T. gigas was carried out in Banyuasin South Sumatra Estuary, Indonesia. The endotoxin test or TAL (Tachypleus amebocyte lysates) assay was performed using gel coagulation method. Protein characterization of protease enzyme was conducted by protease activity, SDS-PAGE, and zymogram analysis. The cDNA of mitochondrial COI gene was amplified for molecular identification followed by cDNA cloning of factor C. Protein modeling was investigated by molecular docking and molecular dynamic (MD) simulation. Endotoxin test results showed that TAL-35 had endotoxin sensitivity in a range of 0.0156–1 EU/ml, while TAL 36 had a sensitivity between 00,625 and 1 EU/ml. T. gigas amebocytes have protease activity in molecular mass sizes less than 60 kDa, with 367 U/ml for TAL 35 and 430 U/ml for TAL 36. The molecular identification revealed 98.68% identity similarity to T. gigas. The docking results suggested three ligands; i.e., diphosphoryl lipid A, core lipid A, and Kdo2 lipid A can be activators of the factor C protein by binding to the region of the receptor to form a ligand-receptor complex. Conclusions Endotoxins can be detected using horseshoe crab amebocytes. The presence of proteases is considered responsible for this ability, as evidenced by casein zymogram results. According to docking and MD analysis, we found that lipopolysaccharides (LPS) participate to the binding site of factor C.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterization, protein modeling, and molecular docking of factor C from Indonesian horseshoe crab (Tachypleus gigas)

Mustopa

Izaki

Suharsono

et al. 2023

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

show abstract

“… 25 The docking parameters were computed according to similar protocols to our previous works. 26 - 28…”

Section: Methodsmentioning

confidence: 99%

Synthesis and initial in vitro evaluation of olmutinib derivatives as prospective imaging probe for non-small cell lung cancer

Fawwaz,

Mishiro,

Arwansyah

et al. 2023

Bioimpacts

View full text Add to dashboard Cite

Introduction: Imaging a non-small cell lung cancer (NSCLC) using radiolabeled tyrosine kinase inhibitors (TKIs) has attracted attention due to their unique interaction with the target epidermal growth factor receptor (EGFR). Olmutinib (OTB) is one of the third-generation EGFR TKIs, which selectively inhibit EGFR L858R/T790M mutation. In this study, we aim to estimate the interaction of the iodinated OTB (I-OTB)-receptor complex by molecular docking. Furthermore, we will synthesize the I-OTB and evaluate its activity toward EGFR L858R/T790M by in vitro cytotoxicity assay. Methods: A molecular docking simulation was carried out using an AutoDock Vina program package to estimate the interaction of the ligand-receptor complex. The I-OTB, N-{3-iodo-5-[(2-{[4-(4-methylpiperazin-1-yl)phenyl]aminothieno{3,2-d}pyrimidin-4-yl)oxy]phenyl} acrylamide, was synthesized by introducing an iodine atom in the phenyl group in the 3-aryloxyanilide structure. The half inhibitory concentration (IC50) was determined by employing a 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt (WST-8) assay to evaluate the activity of I-OTB. Results: The docking study exhibited that I-OTB could take an interaction similar to that of the parent compound. We successfully synthesized I-OTB and confirmed its structure by instrumental analysis. The binding energy of OTB and I-OTB in complex with EGFR T790M are -8.7 and -7.9 kcal/mol, respectively. The cytotoxicity assay showed that I-OTB also has an affinity towards the EGFR L858R/T790M mutation with the IC50 10.49 ± 5.64 𝜇M compared to the EGFR wild type with the IC50 over than 10 𝜇M. Conclusion: The cytotoxicity effect of I-OTB was comparable to that of OTB. This result indicates that the iodine substituent in OTB did not alter the parent compound selectivity toward double mutations EGFR L858R/T790M. Therefore, I-OTB is prominent for radioiodination, and [123/124I]I-OTB may be a promising candidate for EGFR L858R/T790M mutation imaging.

show abstract

“…In performing molecular docking, a grid box parameter is required to decide the positional and rotational of the ligand into the moiety of the receptor (Arwansyah et al 2021a). The grid box was constructed using 24 × 24 26 points and a grid spacing of 1.00 Å.…”

Section: Molecular Dockingmentioning

confidence: 99%

Inhibitory effects of Moringa oleifera leaves extract on xanthine oxidase activity from bovine milk

Natsir¹,

Arif²,

Wahab³

et al. 2022

PHAR

View full text Add to dashboard Cite

Moringa oleifera is a tropical plant in the Moringaceae family that contains a lot of bioactive compounds. This study aimed to isolate and characterize the enzyme xanthine oxidase (XO), and conducted inhibitory tests on XO using methanol extracts of M. oleifera leaves. The xanthine oxidase enzyme isolated from bovine milk was characterized to determine the optimum pH, temperature, and substrate concentration. XO inhibition was evaluated by in vitro and in silico methods. The results of XO isolation and characterization of bovine milk showed the optimum conditions at pH 6.5, substrate concentration of 0.1 mM, and temperature 35 °C with an activity rate of 32.47 mU/mL; 21.55 mU/mL, and 21.94 mU/mL. Inhibition analysis results on methanol extract of M. oleifera leaves showed the highest activity decrease at the extract concentration of 160 ppm, with a relative inhibition value of 21.35%, while allopurinol as a positive control has a relative value inhibition of 61.21%. Relative value inhibition indicated the potential of M. oleifera leaves as a source of medicinal plants for gout sufferers. Additionally, a computational analysis was performed to observe the molecular interaction between the primary compounds of M. oleifera leaves, i.e., 5-O-acetyl-thio-octyl-β-L-rhamnofuranoside, quinic acid, and 2-dimethyl(trimethylsilylmethyl)silyloxymethyltetrahydrofuran, and XO using the molecular docking method. The finding implied that these compounds are bound to the catalytic sites of XO by hydrogen bonds and hydrophobic interactions, indicating the primary compounds of M. oleifera leaves could become XO inhibitors to treat gout disease.

show abstract

Molecular modelling on SARS-CoV-2 papain-like protease: an integrated study with homology modelling, molecular docking, and molecular dynamics simulations

Abstract: Table S1. Databases and software used and their detailed information. Database Name Version Website links References NCBI database Update 2021 https://www.ncbi.nlm.nih.gov/ [1] BLAST database

Cited by 12 publications

References 65 publications

Characterization, protein modeling, and molecular docking of factor C from Indonesian horseshoe crab (Tachypleus gigas)

Characterization, protein modeling, and molecular docking of factor C from Indonesian horseshoe crab (Tachypleus gigas)

Synthesis and initial in vitro evaluation of olmutinib derivatives as prospective imaging probe for non-small cell lung cancer

Inhibitory effects of Moringa oleifera leaves extract on xanthine oxidase activity from bovine milk

Contact Info

Product

Resources

About

Molecular modelling on SARS-CoV-2 papain-like protease: an integrated study with homology modelling, molecular docking, and molecular dynamics simulations

Abstract: Table S1. Databases and software used and their detailed information. Database Name Version Website links References NCBI database Update 2021 https://www.ncbi.nlm.nih.gov/ [1] BLAST database

Cited by 12 publications

References 65 publications

Characterization, protein modeling, and molecular docking of factor C from Indonesian horseshoe crab (Tachypleus gigas)

Characterization, protein modeling, and molecular docking of factor C from Indonesian horseshoe crab (Tachypleus gigas)

Synthesis and initial in vitro evaluation of olmutinib derivatives as prospective imaging probe for non-small cell lung cancer

﻿Inhibitory effects of Moringa oleifera leaves extract on xanthine oxidase activity from bovine milk

Contact Info

Product

Resources

About

Inhibitory effects of Moringa oleifera leaves extract on xanthine oxidase activity from bovine milk