Insilico structural and functional assessment of hypothetical protein L345_13461 from Ophiophagus hannah

Jan, Zainab

doi:10.19045/bspab.2021.100116

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…Our study provides insights into the potential functional consequences of the p.Arg81His substitution in the TMIE gene. Bioinformatics investigation have played pivotal role in genome wide association studies to revolutionizing the identification of mutation [49], their annotation [50], and impact [51], exploration for the discovery of novel and potent drugs [52] along with the identification of molecular targets [53].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Structural Impact and Conformational Dynamics of a Sequence Variant (c.242G>A) inTMIEGene Provoking Usher Syndrome

Ishaq,

Usmani,

Habib

et al. 2024

Preprint

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Usher syndrome (USH) is a retinal autosomal recessive genetic disorder, characterized by congenital severe-to-profound sensorineural hearing loss, retinitis pigmentosa (RP), and rarely vestibular dysfunction. A transmembrane inner ear gene TMIE causing autosomal recessive usher syndrome hearing loss, which may open up interesting perspectives into the function of this protein in inner ear. This disease is linked with mutations in TMIE gene. In this study delineates the pathogenic association, miss-fold aggregation, and conformational paradigm of a missense variant (c.242G>A) resulting into (p.Arg81His) in TMIE gene segregating usher syndrome through a molecular dynamics simulations approach. The transmembrane inner ear expressed protein assumes a critical role as its helices actively engage in binding with specific target DNA base pairs. The alteration observed in the mutant protein, characterized by an outward repositioning of the proximal helical portion, which is attributed to the absence of preceding beta-hairpins in the C-terminal region. This structural modification results in the loss of hydrogen bonds, exposure of hydrophobic residues to the solvent, and a consequential transformation of helices into loops, ultimately leading to functional impairment in the TMIE protein. These notable modifications in the stability and conformation of the mutant protein were verified through essential dynamics analysis, revealing that a point mutation induces distinct overall motions and correlations between proteins, ultimately resulting in usher syndrome. The current study provides insilico evidences of Usher syndrome hearing loss disease as protein folding disorder. The energy calculation also revealed that there is a difference of −251.211Kj/mol which also indicates that the SNP has significantly decreased the stability of protein consequently folding into Usher syndrome. This study contributes molecular insights into the structural correlation between the TMIE protein and usher syndrome. The docking analysis highlight various interaction between wild and mutant structure emphasizing key residues involved in hydrogen and hydrophobic interaction.

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Section: Discussionmentioning

confidence: 99%

Investigating the Structural Impact and Conformational Dynamics of a Sequence Variant (c.242G>A) inTMIEGene Provoking Usher Syndrome

Ishaq,

Usmani,

Habib

et al. 2024

Preprint

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“…Since new therapeutic development is challenging, time-consuming, and costly. Bioinformatics studies have been phenomenal in genome-wide studies (GWAS) to identify mutations (Khattak et al, 2021;Ahmad et al, 2022a), its annotation (Ahmad et al, 2022b;Shah et al, 2022) and impact (Ijaz et al, 2021;Ali et al, 2022a), identification of novel and potent drugs (Ajmal et al, 2022;Ali et al, 2023;Rehman et al, 2023), its targets (Jan et al, 2021) FIGURE 7 The interaction patterns and the fraction of MurF protein in complex with (A) Termstrin B and (B) Fridamycin A through the simulation period. The Histogram plot shows the fraction interaction of each residue, and the colour codes show the type of interaction, i.e., the green colour represents hydrogen bonds, the grey colour represents hydrophobic interactions, the purple colour represents ionic interactions, and the blue colour represents the water bridges.…”

Section: Discussionmentioning

confidence: 99%

Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii

Shoaib

Shehzadi²,

Asif

et al. 2023

Front. Mol. Biosci.

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Multidrug-resistant Acinetobacter baumannii infections have become a major public health concern globally. Inhibition of its essential MurF protein has been proposed as a potential target for broad-spectrum drugs. This study aimed to evaluate the potential of a novel ecological niche of 374 fungus-growing termite associated Natural Products (NPs). The molecular docking and computational pharmacokinetics screened four compounds, i.e., Termstrin B, Fridamycin A, Maduralactomycin A, and Natalenamide C, as potential compounds that have higher binding affinities and favourable protein-ligand interactions. The compound Maduralactomycin A induced more stability based on its lowest average RMSD value (2.31 Å) and low standard deviation (0.35) supported by the consistent flexibility and β-factor during the protein’s time-dependent motion. While hydrogen bond analysis indicated that Termstrin B has formed the strongest intra-protein interaction, solvent accessibility was in good agreement with Maduralactomycin A compactness. Maduralactomycin A has the strongest binding energy among all the compounds (−348.48 kcal/mol) followed by Termstrin B (−321.19 kcal/mol). Since these findings suggest Maduralactomycin A and Termstrin B as promising candidates for inhibition of MurF protein, the favourable binding energies of Maduralactomycin A make it a more important compound to warrant further investigation. However, experimental validation using animal models and clinical trials is recommended before reaching any final conclusions.

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“…Conventional strategies for finding nucleotide changes in genes and their influence on the associated protein in vitro are not only difficult but also slow and arduous to apply. To make things easier, investigations based on computational biology may be carried out [ 57 , 58 ]. SNP stands for single nucleotide polymorphism, and it is the foundation of genetic diversity [ 24 , 25 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Insights into the Role of Pathogenic nsSNPs in GRIN2B Gene Provoking Neurodevelopmental Disorders

Shah

Amjad

Hassan

et al. 2022

Genes

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The GluN2B subunit of N-methyl-D-aspartate receptors plays an important role in the physiology of different neurodevelopmental diseases. Genetic variations in the GluN2B coding gene (GRIN2B) have consistently been linked to West syndrome, intellectual impairment with focal epilepsy, developmental delay, macrocephaly, corticogenesis, brain plasticity, as well as infantile spasms and Lennox–Gastaut syndrome. It is unknown, however, how GRIN2B genetic variation impacts protein function. We determined the cumulative pathogenic impact of GRIN2B variations on healthy participants using a computational approach. We looked at all of the known mutations and calculated the impact of single nucleotide polymorphisms on GRIN2B, which encodes the GluN2B protein. The pathogenic effect, functional impact, conservation analysis, post-translation alterations, their driving residues, and dynamic behaviors of deleterious nsSNPs on protein models were then examined. Four polymorphisms were identified as phylogenetically conserved PTM drivers and were related to structural and functional impact: rs869312669 (p.Thr685Pro), rs387906636 (p.Arg682Cys), rs672601377 (p.Asn615Ile), and rs1131691702 (p.Ser526Pro). The combined impact of protein function is accounted for by the calculated stability, compactness, and total globularity score. GluN2B hydrogen occupancy was positively associated with protein stability, and solvent-accessible surface area was positively related to globularity. Furthermore, there was a link between GluN2B protein folding, movement, and function, indicating that both putative high and low local movements were linked to protein function. Multiple GRIN2B genetic variations are linked to gene expression, phylogenetic conservation, PTMs, and protein instability behavior in neurodevelopmental diseases. These findings suggest the relevance of GRIN2B genetic variations in neurodevelopmental problems.

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Insilico structural and functional assessment of hypothetical protein L345_13461 from Ophiophagus hannah

Cited by 9 publications

References 6 publications

Investigating the Structural Impact and Conformational Dynamics of a Sequence Variant (c.242G>A) inTMIEGene Provoking Usher Syndrome

Investigating the Structural Impact and Conformational Dynamics of a Sequence Variant (c.242G>A) inTMIEGene Provoking Usher Syndrome

Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii

Molecular Insights into the Role of Pathogenic nsSNPs in GRIN2B Gene Provoking Neurodevelopmental Disorders

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