Computational Study of Thymine Dimer Radical Anion Splitting in the Self-Repair Process of Duplex DNA.
Formation of the thymine dimer is one of the most important types of photochemical damage in DNA, responsible for several biological pathologies. Though specifically designed proteins (photolyases) can efficiently repair this type of damage in living cells, an autocatalytic activity of the DNA itsel...
| Published in: | Journal of the American Chemical Society Vol. 130; no. 11; pp. 3443 - 3451 |
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| Main Authors: | , , , , |
| Format: | Article |
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American Chemical Society
3/19/2008
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| Subjects: | |
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=31445774&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 31445774 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 3/19/2008 vid: 130 iid: 11 pid: 997 pub: American Chemical Society artinfo: ui: 31445774 10.1021/ja076081h ppf: 3443 ppct: 8 formats: tig: atl: Computational Study of Thymine Dimer Radical Anion Splitting in the Self-Repair Process of Duplex DNA. aug: au: Masson, Fanny Laino, Teodoro Tavernelli, Ivano Rothlisberger, Ursula Hutter, Jürg affil: Physikalisch Chemisches Institut, Universität Zürich, Winrerthurerstrasse 190, CH-8057 Zürich, Switzerland Laboratory of Computational Chemistry and Biochemistry, Federal Institute of Technology, EPFL, CH-1015 Lausanne, Switzerland su: Thymine DNA Proteins Density functionals Molecular dynamics Functional analysis sug: subj: Thymine DNA Proteins Density functionals Molecular dynamics Functional analysis ab: Formation of the thymine dimer is one of the most important types of photochemical damage in DNA, responsible for several biological pathologies. Though specifically designed proteins (photolyases) can efficiently repair this type of damage in living cells, an autocatalytic activity of the DNA itself was recently discovered, allowing for a self-repair mechanism. In this paper, we provide the first molecular dynamics study of the splitting of thymine dimer radical anions, using a quantum mechanical/molecular mechanics (QM/MM) approach based on density functional theory (OFT) to describe the quantum region. A set of seven statistically representative molecular dynamics trajectories is analyzed. Our calculations predict an asynchronously concerted process in which C5-C5′ bond breaking is barrierless while C6-C6′ bond breaking is characterized by a small free energy barrier. An upper bound of 2.5 kcal/mol for this barrier is estimated. Moreover, the molecular dynamics study and the low free energy barrier involved in C6-C6′ bond breaking characterize the full process as being an ultrafast reaction. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2008 holdings: @attributes: islocal: N |
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