دورية أكاديمية
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A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics.

التفاصيل البيبلوغرافية
العنوان: A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics.
المؤلفون: Saxena S; Department of Biotechnology, Ramaiah Institute of Technology, Bengaluru, Karnataka, 560054, India., Krishna Murthy TP; Department of Biotechnology, Ramaiah Institute of Technology, Bengaluru, Karnataka, 560054, India. tpk@live.in., Chandrashekhar CR; Department of Biotechnology, Ramaiah Institute of Technology, Bengaluru, Karnataka, 560054, India., Patil LS; Department of Biotechnology, Ramaiah Institute of Technology, Bengaluru, Karnataka, 560054, India., Aditya A; Department of Biotechnology, Ramaiah Institute of Technology, Bengaluru, Karnataka, 560054, India., Shukla R; Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Solan, Himachal Pradesh, 173234, India., Yadav AK; Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Solan, Himachal Pradesh, 173234, India., Singh TR; Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology (JUIT), Solan, Himachal Pradesh, 173234, India., Samantaray M; Department of Bioinformatics, Pondicherry University, Pondicherry, 605014, India., Ramaswamy A; Department of Bioinformatics, Pondicherry University, Pondicherry, 605014, India.
المصدر: Scientific reports [Sci Rep] 2022 Nov 07; Vol. 12 (1), pp. 18872. Date of Electronic Publication: 2022 Nov 07.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Computational Biology* , Methyltransferases*/genetics, Humans ; Genotype ; Molecular Dynamics Simulation ; Mutation ; Polymorphism, Single Nucleotide
مستخلص: Polymorphisms of Thiopurine S-methyltransferase (TPMT) are known to be associated with leukemia, inflammatory bowel diseases, and more. The objective of the present study was to identify novel deleterious missense SNPs of TPMT through a comprehensive in silico protocol. The initial SNP screening protocol used to identify deleterious SNPs from the pool of all TPMT SNPs in the dbSNP database yielded an accuracy of 83.33% in identifying extremely dangerous variants. Five novel deleterious missense SNPs (W33G, W78R, V89E, W150G, and L182P) of TPMT were identified through the aforementioned screening protocol. These 5 SNPs were then subjected to conservation analysis, interaction analysis, oncogenic and phenotypic analysis, structural analysis, PTM analysis, and molecular dynamics simulations (MDS) analysis to further assess and analyze their deleterious nature. Oncogenic analysis revealed that all five SNPs are oncogenic. MDS analysis revealed that all SNPs are deleterious due to the alterations they cause in the binding energy of the wild-type protein. Plasticity-induced instability caused by most of the mutations as indicated by the MDS results has been hypothesized to be the reason for this alteration. While in vivo or in vitro protocols are more conclusive, they are often more challenging and expensive. Hence, future research endeavors targeted at TPMT polymorphisms and/or their consequences in relevant disease progressions or treatments, through in vitro or in vivo means can give a higher priority to these SNPs rather than considering the massive pool of all SNPs of TPMT.
(© 2022. The Author(s).)
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المشرفين على المادة: EC 2.1.1.- (Methyltransferases)
EC 2.1.1.67 (TPMT protein, human)
تواريخ الأحداث: Date Created: 20221107 Date Completed: 20221114 Latest Revision: 20230105
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9640560
DOI: 10.1038/s41598-022-23488-z
PMID: 36344599
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-022-23488-z