Prediction of functionally significant single nucleotide polymorphisms in PTEN tumor suppressor gene: An in silico approach

Biotechnology and Applied Biochemistry
Imran KhanFebin Prabhu Dass J

Abstract

The phosphatase and tensin homolog (PTEN) gene plays a crucial role in signal transduction by negatively regulating the PI3K signaling pathway. It is the most frequent mutated gene in many human-related cancers. Considering its critical role, a functional analysis of missense mutations of PTEN gene was undertaken in this study. Thirty five nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of the PTEN gene were selected for our in silico investigation, and five nsSNPs (G129E, C124R, D252G, H61D, and R130G) were found to be deleterious based on combinatorial predictions of different computational tools. Moreover, molecular dynamics (MD) simulation was performed to investigate the conformational variation between native and all the five mutant PTEN proteins having predicted deleterious nsSNPs. The results of MD simulation of all mutant models illustrated variation in structural attributes such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and total energy; which depicts the structural stability of PTEN protein. Furthermore, mutant PTEN protein structures also showed a significant variation in the solvent accessible surface area and hydrogen bond frequencies from the ...Continue Reading

References

Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M PrevostM Karplus
Dec 1, 1987·Protein Engineering·M Vihinen
Jan 16, 1986·Nature·D Eisenberg, A D McLachlan
Jan 1, 1984·Progress in Biophysics and Molecular Biology·E N Baker, R E Hubbard
Sep 29, 1995·Journal of Molecular Biology·V I AbkevichE I Shakhnovich
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Jun 24, 2000·Molecular and Cellular Biology·F VazquezW R Sellers
Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Mar 7, 2001·Human Molecular Genetics·S SunyaevP Bork
Apr 11, 2001·Human Mutation·Z Wang, J Moult
May 5, 2001·Genome Research·P C Ng, S Henikoff
Mar 5, 2002·American Journal of Human Genetics·Kristin A Waite, Charis Eng
Aug 31, 2002·Nucleic Acids Research·Vasily RamenskyShamil Sunyaev
Jan 9, 2003·Trends in Biochemical Sciences·Valerie Daggett, Alan R Fersht
Dec 19, 2003·Nucleic Acids Research·K Abdulla BavaAkinori Sarai
Aug 4, 2004·Progress in Biophysics and Molecular Biology·M Michael Gromiha, S Selvaraj
Dec 21, 2004·Nucleic Acids Research·Huaiyu MiPaul D Thomas
Nov 4, 2005·Journal of Cellular Biochemistry·Jin-Tang Dong
May 16, 2006·Structure·Jung-Hoon HanSarah A Teichmann
Aug 22, 2007·BMC Bioinformatics·David F BurkeTom L Blundell
May 14, 2008·Current Cancer Drug Targets·Amancio CarneroJuan F M Leal
Mar 17, 2010·Trends in Genetics : TIG·Norann A Zaghloul, Nicholas Katsanis
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 5, 2013·Cell Biochemistry and Biophysics·A Sai RameshPadma Thiagarajan

❮ Previous
Next ❯

Citations

May 20, 2017·Journal of Cellular Biochemistry·William Farias PortoRobert Pogue
Oct 9, 2019·JCO Precision Oncology·Verena SailerHimisha Beltran
May 19, 2020·International Journal of Peptide Research and Therapeutics·Sobia Ahsan HalimAhmed Al-Harrasi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.