Analyzing effects of naturally occurring missense mutations.

Computational and Mathematical Methods in Medicine
Zhe ZhangEmil Alexov

Abstract

Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causing mutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well.

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Citations

Mar 8, 2013·PLoS Computational Biology·Zhe ZhangEmil Alexov
Jul 17, 2013·Journal of Molecular Biology·Virginie Y Martiny, Maria A Miteva
Jun 13, 2015·Nucleic Acids Research·Kenneth F LyonMartin R Schiller
Feb 7, 2015·Current Opinion in Structural Biology·Tugba G KucukkalEmil Alexov
Jul 23, 2013·Journal of Molecular Biology·Shannon SteflEmil Alexov
Jan 27, 2015·Human Genetics·Mauno Vihinen
Mar 19, 2016·Human Mutation·Abhishek Niroula, Mauno Vihinen
Apr 15, 2016·International Journal of Molecular Sciences·Marharyta PetukhEmil Alexov
Feb 18, 2017·International Journal of Molecular Sciences·Maria PetrosinoRoberta Chiaraluce
May 23, 2013·Human Molecular Genetics·Zhe ZhangHilde Van Esch
Jun 1, 2017·Scientific Reports·Allan S PiresSérgio A Alencar
May 22, 2013·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Xabier Arias-MorenoJose F Lucía
May 21, 2021·Human Mutation·Mónica Lopes-MarquesLuísa Azevedo
May 28, 2021·Biochimica Et Biophysica Acta. General Subjects·Wendy S MendesWilliam F Porto
Aug 6, 2021·Computers in Biology and Medicine·Sidharth SaxenaTiratha Raj Singh
Sep 8, 2021·Frontiers in Molecular Biosciences·Kuan Pern TanMallur Srivatsan Madhusudhan
Nov 2, 2021·Frontiers in Immunology·Wirawan AdikusumaWei-Chiao Chang

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Methods Mentioned

BETA
in silico methods
protein folding

Software Mentioned

DrugScore
TANGO )
AUTO
SIFT
Eris webserver
TINKER
JACKAL package
Mutant
Polyphen
StSNP

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