Recognition of a tandem lesion by DNA bacterial formamidopyrimidine glycosylases explored combining molecular dynamics and machine learning.

Computational and Structural Biotechnology Journal
Emmanuelle BignonElise Dumont

Abstract

The combination of several closely spaced DNA lesions, which can be induced by a single radical hit, constitutes a hallmark in the DNA damage landscape and radiation chemistry. The occurrence of such a tandem base lesion gives rise to a strong coupling with the double helix degrees of freedom and induces important structural deformations, in contrast to DNA strands containing a single oxidized nucleobase. Although such complex lesions are known to be refractory to repair by DNA glycosylases, there is still a lack of structural evidence to rationalize these phenomena. In this contribution, we explore, by numerical modeling and molecular simulations, the behavior of the bacterial glycosylase responsible for base excision repair (MutM), specialized in excising oxidatively-damaged defects such as 7,8-dihydro-8-oxoguanine (8-oxoG). The difference in lesion recognition between a simple damage and a tandem lesion featuring an additional abasic site is assessed at atomistic resolution owing to microsecond molecular dynamics simulations and machine learning postprocessing, allowing to extensively pinpoint crucial differences in the interaction patterns of the damaged bases. Our results reveal substantial changes in the interaction netwo...Continue Reading

References

Jan 1, 1985·Clinics in Dermatology·K H Kraemer, H Slor
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 26, 2002·The Journal of Biological Chemistry·Rotem GilboaGil Shoham
Oct 4, 2003·The Journal of Biological Chemistry·J Christopher Fromme, Gregory L Verdine
Nov 26, 2003·Mutation Research·P FortiniE Dogliotti
Jul 27, 2004·Protein Science : a Publication of the Protein Society·Patricia AmaraAline Thomas
Apr 5, 2005·Journal of Computational Chemistry·Hirofumi FujimotoHideaki Maekawa
Mar 6, 2007·Journal of the American Chemical Society·In Seok HongMarc M Greenberg
Jun 22, 2007·Nature·Sheila S DavidSucharita Kundu
Oct 28, 2008·Biochemistry·Raphael D HazelCarlos de Los Santos
Jul 25, 2009·Nucleic Acids Research·R LaveryK Zakrzewska
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·François BergeronJean-Luc Ravanat
May 18, 2010·Biochemistry·Joshua I Friedman, James T Stivers
Sep 22, 2010·Journal of Chemical Theory and Computation·Martin B PetersKenneth M Merz
Aug 13, 2011·Accounts of Chemical Research·Alberto PérezModesto Orozco
Mar 13, 2012·International Journal of Medical Sciences·Rajamanickam BaskarKheng-Wei Yeoh
Sep 20, 2012·The Journal of Biological Chemistry·Akira SassaSamuel H Wilson
Feb 5, 2013·Cold Spring Harbor Perspectives in Biology·Jean Cadet, J Richard Wagner
May 21, 2013·Radiation Research·Alexandros G GeorgakilasRobert D Stewart
Jul 16, 2013·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Julien VignardBernard Salles
May 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Shane R NelsonSusan S Wallace
Jul 30, 2014·Angewandte Chemie·Keyarash SadeghianChristian Ochsenfeld
Nov 11, 2015·Nucleic Acids Research·Haoquan LiCarlos Simmerling
Nov 17, 2015·Nature Methods·Ivan IvaniModesto Orozco
Nov 18, 2015·Journal of Chemical Theory and Computation·James A MaierCarlos Simmerling
Feb 21, 2016·Pharmacology & Therapeutics·Navnath S GavandeJohn J Turchi
Jun 21, 2016·Current Protocols in Bioinformatics·Benjamin Webb, Andrej Sali
Jul 22, 2016·Chemistry : a European Journal·Elise DumontIñaki Tuñón
Sep 10, 2016·The Journal of Physical Chemistry Letters·Hugo GattusoAntonio Monari
Dec 13, 2016·Free Radical Biology & Medicine·Evelyne Sage, Naoya Shikazono
May 10, 2017·Environmental and Molecular Mutagenesis·Nimrat Chatterjee, Graham C Walker
Mar 24, 2018·International Journal of Molecular Sciences·Ashis K Basu
Mar 27, 2018·Journal of the American Chemical Society·Andrea KreppelChristian Ochsenfeld

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Software Mentioned

Ambertools
MutM
Curves +
R
Amber
ggplot2 package of
Modeller

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