Genome-wide identification and analysis of GRF (growth-regulating factor) gene family in Camila sativa through in silico approaches

Zafar, Imran; Rubab, Alia; Aslam, Maryam; Ahmad, Syed Umair; Liaqat, Iqra; Malik, Abdul; Alam, Mahboob; Wani, Tanveer A.; Khan, Azmat Ali

doi:10.1016/j.jksus.2022.102038

Cited by 14 publications

(3 citation statements)

References 45 publications

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“…genecards.org/), and UniPort (https://www.uniprot.org/), which are periodically refreshed with new information. In particular, the ENSEMBLE repository was availed to obtain the nucleotide and protein sequences germane to the HRAS gene as per the methods of earlier researchers (Buljan et al, 2018;Zafar et al, 2022). This undertaking holds the promise of research prospects for exploring genetic variations and their potential implications (Rajaram et al, 2001).…”

Section: Collecting and Preparing Snp Datamentioning

confidence: 99%

Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function

Ali¹,

Ali²,

Qamar³

et al. 2023

Front. Chem.

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The HRAS gene plays a crucial role in regulating essential cellular processes for life, and this gene's misregulation is linked to the development of various types of cancers. Nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of HRAS can cause detrimental mutations that disrupt wild-type protein function. In the current investigation, we have employed in-silico methodologies to anticipate the consequences of infrequent genetic variations on the functional properties of the HRAS protein. We have discovered a total of 50 nsSNPs, of which 23 were located in the exon region of the HRAS gene and denoting that they were expected to cause harm or be deleterious. Out of these 23, 10 nsSNPs ([G60V], [G60D], [R123P], [D38H], [I46T], [G115R], [R123G], [P11OL], [A59L], and [G13R]) were identified as having the most delterious effect based on results of SIFT analysis and PolyPhen2 scores ranging from 0.53 to 69. The DDG values −3.21 kcal/mol to 0.87 kcal/mol represent the free energy change associated with protein stability upon mutation. Interestingly, we identified that the three mutations (Y4C, T58I, and Y12E) were found to improve the structural stability of the protein. We performed molecular dynamics (MD) simulations to investigate the structural and dynamic effects of HRAS mutations. Our results showed that the stable model of HRAS had a significantly lower energy value of −18756 kj/mol compared to the initial model of −108915 kj/mol. The RMSD value for the wild-type complex was 4.40 Å, and the binding energies for the G60V, G60D, and D38H mutants were −107.09 kcal/mol, −109.42 kcal/mol, and −107.18 kcal/mol, respectively as compared to wild-type HRAS protein had −105.85 kcal/mol. The result of our investigation presents convincing corroboration for the potential functional significance of nsSNPs in augmenting HRAS expression and adding to the activation of malignant oncogenic signalling pathways.

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Section: Collecting and Preparing Snp Datamentioning

confidence: 99%

Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function

Ali¹,

Ali²,

Qamar³

et al. 2023

Front. Chem.

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“…Multiple sequence alignment was performed to trace the conserved region of the target candidate gene through the time of evolution in humans. For this purpose, the genome of six MAPK1 strains was retrieved to build a neighbour-joining tree using an evolutionary tool (MEGAX) as per the method of earlier researchers [ 49 , 50 ]. The observation shows the binding domain or active site was conserved among all MAPK1 strains.…”

Section: Discussionmentioning

confidence: 99%

In silico designing of multiepitope-based-peptide (MBP) vaccine against MAPK protein express for Alzheimer's disease in Zebrafish

Arfat,

Zafar,

Sehgal

et al. 2023

Heliyon

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“…In this rigorous investigation, we acquired the FASTA-formatted amino acid sequences of vital proteins, namely CDK4, EGFR, RAS, BRAF, PTEN, and PI3K, from UniProt ( Zafar et al, 2022 ; Ali et al, 2023b ). To determine suitable templates for these target proteins, a comprehensive Protein Data Bank search was performed using BLASTp as per the method of ( Mahram and Herbordt, 2015 ; Dana et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

Zafar,

Safder,

Imran Afridi

et al. 2023

Front. Chem.

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Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments.Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability.Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C −80, C-120,C −150, C −200 ns) revealed strong hydrogen bonding in the complexes and showed −12.9, −11.6, and −11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis.Conclusion:Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

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Genome-wide identification and analysis of GRF (growth-regulating factor) gene family in Camila sativa through in silico approaches

Cited by 14 publications

References 45 publications

Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function

Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function

In silico designing of multiepitope-based-peptide (MBP) vaccine against MAPK protein express for Alzheimer's disease in Zebrafish

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer

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