Assessment of structurally and functionally high-risk nsSNPs impacts on human bone morphogenetic protein receptor type IA (BMPR1A) by computational approach

Islam, Md. Jahirul; Parves, Md. Rimon; Mahmud, Shafi; Tithi, Fahmida Alam; Reza, Abu

doi:10.1016/j.compbiolchem.2019.03.004

Cited by 30 publications

(16 citation statements)

References 50 publications

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“…The simulation result was incorporated with the default script of YASARA. Finally, root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and Hydrogen bonds (H-bonds) were analyzed (Islam et al., 2019 ; Khan et al., 2020 ; Mahmud et al., 2020a, 2020b ). To have more correct result from molecular dynamics simulation, each complex were run thrice (n=3) and average result was used for analysis.…”

Section: Methodsmentioning

confidence: 99%

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Swargiary

Mahmud

Saleh

2020

Journal of Biomolecular Structure and Dynamics

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COVID-19 and its causative organism SARS-CoV2 that emerged from Wuhan city, China have paralyzed the world. With no clinically approved drugs, the global health system is struggling to find an effective treatment measure. At this crucial juncture, screening of plant-derived compounds may be an effective strategy to combat COVID-19. The present study investigated the binding affinity of phytocompounds with 3-Chymotrypsin-like (3CLpro) and Papain-like proteases (PLpro) of SARS-CoV2 using in-silico techniques. A total of 32 anti-protease phytocompounds were investigated for the binding affinity to the proteins. Docking was performed in Autodock Vina. Pharmacophore descriptors of best ligands were studied using LigandScout. Molecular dynamics (MD) simulation of apo-protein and ligand-bound complexes was carried out in YASARA software. The druglikeness properties of phytocompounds were studied using ADMETlab. Out of 32 phytochemicals, amentoflavone and gallocatechin gallate showed the best binding affinity to 3CLpro (–9.4 kcal/mol) and PLpro (–8.8 kcal/mol). Phytochemicals such as savinin, theaflavin-3,3-digallate, and kazinol-A also showed strong affinity. MD simulation revealed ligand-induced conformational changes in the protein with decreased surface area and higher stability. The RMSD/F of proteins and ligands showed stability of the protein suggesting the effective binding of the ligand in both the proteins. Both amentoflavone and gallocatechin gallate possess promising druglikeness property. The present study thus suggests that Amentoflavone and Gallocatechin gallate may be potential inhibitors of 3CLpro and PLpro proteins and effective drug candidates for SARS-CoV2. However, the findings of in silico study need to be supported by in vivo studies to establish the exact mode of action. Communicated by Ramaswamy H. Sarma

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Section: Methodsmentioning

confidence: 99%

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Swargiary

Mahmud

Saleh

2020

Journal of Biomolecular Structure and Dynamics

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“…Molecular modelling especially docking and dynamic simulation study has become essential part in modern drug discovery pipeline(Bappy et al., 2020 ; Elfiky, 2020a ; Islam et al., 2019 ). Moreover, time and lab cost can significantly reduce by narrowing the drug molecule choices in in silico based drug discovery process (Talele et al., 2010 ).…”

Section: Discussionmentioning

confidence: 99%

“…Molecular dynamics study of screened drug molecules were checked to evaluate their stability at atomic scale. The average root mean square deviation (RMSD) of Epirubicin, Vapreotida, Saquinavir are 1.756, 2.008, 1.76 Å which indicates complex stability throughout the entire simulation (Islam et al., 2019 ). Additionally, the average radius of gyration for these three complexes were found as 22.307, 22.211, 22.301 Å and did not deviate much.…”

Section: Discussionmentioning

confidence: 99%

Comparative molecular investigation of the potential inhibitors against SARS-CoV-2 main protease: a molecular docking study

Khan

Mahmud

Alam³

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Recent outbreak of novel coronavirus and its rapid pandemic escalation in all over the world has drawn the attention to urgent need for effective drug development. However, due to prolonged vaccine and drug development procedure against a newly emerged devastating SARS-CoV-2 virus pathogen, repurposing of existing potential pertinent drug molecules would be preferable strategy to reduce mortality immediately and further development of new drugs to combat overall global Covid-19 crisis in all over the world. Herein, we have filtered 23 prospective drug candidates through literature review. Assessing evidences from molecular docking studies, it was clearly seen that, Epirubicin, Vapreotida, and Saquinavir exhibited better binding affinity against SARS-CoV-2 Main Protease than other drug molecules among the 23 potential inhibitors. However, 50 ns molecular dynamics simulation indicated the less mobile nature of the docked complex maintaining structural integrity. Our overall prediction findings indicate that Epirubicin, Vapreotida, and Saquinavir may inhibit COVID-19 by synergistic interactions in the active cavity and those results can pave the way in drug discovery although it has to be further validated by in-vitro and in-vivo investigations.

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“…Our computational strategy was similar to that used by different previous studies [21–23] which includes the prediction of deleterious nsSNPs in LEP gene from the public datasets using various bioinformatics tools. High-risk nsSNPs were further selected for conservational, stability, and structural analysis.…”

Section: Methodsmentioning

confidence: 99%

Prediction and Structural Comparison of Deleterious Coding Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Human LEP Gene Associated with Obesity

Bouafi

Bencheikh

Krami

et al. 2019

BioMed Research International

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Leptin is a peptide hormone that regulates fat stores in the body and appetite by controlling the feeling of satiety. This hormone is secreted by the white adipose tissue and plays a role in the storage and mobilization of fatty acids. Mutations of the LEP gene have been associated with obesity in different populations; it is a multifactorial disease that constitutes a major public health problem. In this study, we evaluated the impact of missense SNPs in the LEP gene extracted from dbSNP using 8 computational prediction tools. Out of the total of 4337 SNPs, 93 were nsSNPs (nonsynonymous single nucleotide polymorphisms). Among 93 nsSNPs, 12 (S46L, G59S, D61N, D100N, N103K, C117S, D76V, S88C, P90R, I95N, L161R, and R105W) variants were predicted to be the most deleterious by prediction software. On these 12 deleterious SNPs, 8 variants (S46L, G59S, D61N, D100N, N103K, C117S, L161R, and R105W) were located in the conserved positions and showed a decrease in structure stability which was evaluated by I-Mutant and Mupro. Then, by analyzing the different interactions between different amino acids in wild and mutated proteins, we assessed the structural impact of the deleterious modifications using the YASARA software. Among 8 deleterious nsSNPs, we revealed structure changes in the 6 variants S46L, G59S, D100N, L103K, R105W, L161R, two of which R105W, N103K were previously reported as associated with obesity. Our study suggests 6 deleterious mutations could play an important role in contributing to human obesity and worth to be included in association and functional studies, then may be a drug target.

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Assessment of structurally and functionally high-risk nsSNPs impacts on human bone morphogenetic protein receptor type IA (BMPR1A) by computational approach

Cited by 30 publications

References 50 publications

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Screening of phytochemicals as potent inhibitor of 3-chymotrypsin and papain-like proteases of SARS-CoV2: an in silico approach to combat COVID-19

Comparative molecular investigation of the potential inhibitors against SARS-CoV-2 main protease: a molecular docking study

Prediction and Structural Comparison of Deleterious Coding Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Human LEP Gene Associated with Obesity

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