In-silico analysis of non-synonymous-SNPs of STEAP2: To provoke the progression of prostate cancer

Naveed, Muhammad; Tehreem, Sana; Mubeen, Shamsa; Nadeem, Fareeha; Zafar, Fatima; Irshad, Muhammad

doi:10.1515/biol-2016-0054

Cited by 36 publications

(12 citation statements)

References 64 publications

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“…A study analyzed genetic variations in ABCA1 gene and predicted their deleterious effects causing familial hypoalphalipoproteinemia and tangier disease [ 16 ]. Similar study identified missense SNPs in STEAP2 which cause its upregulation leading to prostate cancer [ 17 ]. The nsSNPs in NKX2-5 gene were found associated with congenital heart defects because of their damaging effects on structural features of the protein [ 18 ].…”

Section: Introductionmentioning

confidence: 81%

Identification and in silico analysis of functional SNPs of human TAGAP protein: A comprehensive study

2018

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Genetic polymorphisms in TAGAP gene have been associated with many diseases including rheumatoid arthritis, multiple sclerosis and other autoimmune disorders. Identifying functional SNPs in such disease associated genes is an uphill task hence before planning larger population study, it is better to scrutinize putative functional SNPs. In this study we used various computational approaches to identify nsSNPs which are deleterious to the structure and/or function of TAGAP protein that might be causing these diseases. Computational analysis was performed by five different in silico tools including SIFT, PROVEAN, PolyPhen-2, PhD-SNP and SNPs&GO. The study concludes that mutations of Glycine → Glutamic Acid at position 120, Glycine → Tryptophan at position 141 and Valine → Methionine at position 151 are major mutations in native TAGAP protein which might contribute to its malfunction and ultimately causing disease. The study also proposed 3D structures of native TAGAP protein and its three mutants. Future studies should consider these nsSNPs as main target mutations in various diseases involving TAGAP malfunction. This is the first comprehensive study, where TAGAP gene variants were analyzed using in silico tools hence will be of great help while considering large scale studies and also in developing precision medicines for cure of diseases related to these polymorphisms. Furthermore, animal models of various autoimmune diseases and having these mutations might be of help in exploring their precise roles.

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Section: Introductionmentioning

confidence: 81%

Identification and in silico analysis of functional SNPs of human TAGAP protein: A comprehensive study

2018

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“…Deleterious effects resulted from genetic variations were predicted in ABCA1 gene in a study which could lead to tangier and hypoalphalipoproteinemia disease (MarõÂn‐MartõÂn, Soler‐Rivas, MartõÂn‐HernaÂndez, & Rodriguez‐Casado, ). In STEAP2 gene, nsSNPs, which could lead upregulation in the said gene and result in prostate cancer, were identified in a similar study (Naveed et al, ). Congenital heart diseases were found to be associated with NKX2‐5 gene, in which protein structural features could possibly be damaged by nsSNPs (Samad, Suliman, Basha, Manivasagam, & Essa, ).…”

Section: Introductionmentioning

confidence: 77%

Identification of most damaging nsSNPs in human CCR6 gene: In silico analyses

Akhtar

Jamal

Jamal³

et al. 2019

Int J Immunogenetics

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Single nucleotide polymorphisms in CCR6 (C–C chemokine receptor type 6) gene have been found to be the possible cause of many diseases like rheumatoid arthritis, psoriasis, lupus nephritis and systemic sclerosis and other autoimmune diseases. Therefore, identification of structurally and functionally important polymorphisms in CCR6 is important in order to study its potential malfunctioning and discovering therapeutic targets. Several bioinformatics tools were used to identify most damaging nsSNPs that might be vital for CCR6 structure and function. The in silico tools included PROVEAN, SIFT, SNP&GO and PolyPhen2 followed by I‐Mutant MutPred and ConSurf. Phyre2 and I‐TASSER were used for protein 3‐D Modelling while gene–gene interaction was predicted by STRING and GeneMANIA. Our study suggested that three nsSNPs https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1376162684, https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=751102128 and https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1185426631 are the most damaging in CCR6 gene while 7 missense SNPs https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1438637216, https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=139697820, https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=768420505, https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1282264186, https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1394647982, https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=769360638 and https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1263402382 are found to revert into stop codons. Prediction of post‐transcriptional modifications highlighted the significance of https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1376162684 because it effected potential phosphorylation site. Gene–gene interactions showed relation of CCR6 with other genes depicting its importance in several pathways and co‐expressions. In future, studying diseases related to CCR6 should include investigation of these 10 nsSNPs. Being the first of its type, this study also proposes future perspectives that will help in precision medicines. For such purposes, CCR6 proteins from patients of autoimmune diseases should be explored. Animal models can also be of significance find out the effects of CCR6 in diseases.

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“…Two strong hydrogen bonds were established with Asp-2357 and Tyr-2225 ( Figure 5). Hydrogen bonding with these residues is a cause of increase in potency as reported by [23,30,31].…”

Section: Docking Analysis Of Azd 2014mentioning

confidence: 82%

Molecular Docking and Pharmacokinetic of Highly Specific Novel Pan-Mtor Inhibitors against Solid Tumors

Naveed¹

2017

MOJPB

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Mechanistic/mammalian target of rapamycin (mTOR) a serine/threonine kinase belonging to PI3K/Akt/mTOR pathway is involved in different cellular functions cell survival, metabolism, growth, proliferation, apoptosis and autophagy. PanmTOR inhibitors are targeted towards mTOR dysregulation, inhibiting the kinase domain of both mTORC1 and mTORC2. The present study analyzes the binding modes and molecular interactions of highly specific mTOR inhibitors, AZD8055 and its sister compoundAZD2014using computational approach. Both inhibitors proved to be effective against solid tumors in vitro and in vivo. Docking analysis was performed using Auto Dock Vina, conformations were scored based upon their binding energy (kcal/mol) and illustrated using Discovery Studio Visualizer 4.5 version. Inhibitors fit between N-and C-lobes of mTOR kinase domain into the inner hydrophobic core. The results indicated interactions with distinctive mTOR residues Trp-2239, Leu-2185 and newly developed interactions with Asp-2375 for AZD2014 and with Ala-2248, His-2247, Thr-2245 for AZD8055. The binding pattern of both inhibitors was slightly different, responsible for better pharmacokinetic profile of AZD2014 and 5 fold increase in efficacy of AZD8055. The binding energy of best docking score for AZD8055 was -8.0 kcal/mol however AZD20144 showed best binding affinity at -8.2kcal/mol (RMSD l.b. 0.908, RMSD u.b. 1.075). Highly specific, less toxic and potent inhibitors can be designed or optimized based upon the docking results.

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In-silico analysis of non-synonymous-SNPs of STEAP2: To provoke the progression of prostate cancer

Cited by 36 publications

References 64 publications

Identification and in silico analysis of functional SNPs of human TAGAP protein: A comprehensive study

Identification and in silico analysis of functional SNPs of human TAGAP protein: A comprehensive study

Identification of most damaging nsSNPs in human CCR6 gene: In silico analyses

Molecular Docking and Pharmacokinetic of Highly Specific Novel Pan-Mtor Inhibitors against Solid Tumors

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