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Theoretical studies on photophysics and photochemistry of DNA
KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Theoretical studies on biological systems like nucleic acid and protein have been widely developed in the past 50 years and will continue to be a topic of interest in forefronts of natural science. In addition to experimental science, computational modeling can give useful information and help us to understand biochemical issues at molecular, atomic and even electronic levels.

Deoxyribonucleic acid (DNA), the hereditary basis of life’s genetic identity, has always been major topic of discussions since its structure was built in 1953. However, harmful UV radiation from sunlight can make damage to DNA molecules and eventually give rise to DNA damaging biological consequences, like mutagenesis, carcinogenesis, and cell death. Photostability, photodamage, and photorepair are of vital importance in the photophysics and photochemistry of DNA. In this thesis, we have applied high level computer-aided theoretical methods to explore the underlying mechanisms for these three critical issues of DNA. Special attentions are paid to the following aspects: the properties of the excited states, the design of relevant computational models and the effects of biological environments.

We have systematically studied the excited state properties of DNA from single base to base pair and oligonucleotides, where the concerted base pairing and base stacking effects was found to play important roles in DNA photostability. The UV-light induced isomerization mechanism between two photoproducts of DNA photodamage has been revealed in different biological environments. In association with DNA photodamage, the related photorepair processes have been proposed for different lesions in photolyase which is a catalytic enzyme for DNA, and the calculated results well explained the experimental observations. In particular, the internal and external properties of flavin cofactors have been extensively studied by combining the electronic structure and spectroscopic calculations. We have examined the effects of the intramolecular hydrogen bond on spectroscopic properties of flavins. The good agreements with the experimental spectra indicated that the biological self-regulation acted critical role in these biological systems.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology , 2010. , 76 p.
Series
Trita-BIO-Report, ISSN 1654-2312 ; 2011:15
National Category
Theoretical Chemistry
Research subject
SRA - Molecular Bioscience
Identifiers
URN: urn:nbn:se:kth:diva-33531ISBN: 978-91-7415-977-6OAI: oai:DiVA.org:kth-33531DiVA: diva2:416168
Public defence
2011-06-14, FA32, AlbaNova University Center, Roslagstullsbacken 21,, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
QC 20110530Available from: 2011-05-30 Created: 2011-05-09 Last updated: 2011-05-30Bibliographically approved
List of papers
1. Exploring concerted effects of base pairing and stacking on the excited-state nature of DNA oligonucleotides by DFT and TD-DFT studies
Open this publication in new window or tab >>Exploring concerted effects of base pairing and stacking on the excited-state nature of DNA oligonucleotides by DFT and TD-DFT studies
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2011 (English)In: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 111, no 10, 2366-2377 p.Article in journal (Refereed) Published
Abstract [en]

We have taken (dA)5, (dT)5, and (dA)5•(dT)5 as model systems to study concerted effects of base pairing and stacking on excited-state nature of DNA oligonucleotides using density functional theory (DFT) and time dependent DFTmethods. The spectroscopic states are determined to be of a partial A →A charge transfernature in the A•T oligonucleotides. The T → T charge-transfer transitionsproduce dark states, which are hidden in the energy region of the steady-stateabsorption spectra. This is different from the previous assignment that the T → Tcharge-transfer transition is responsible for a shoulder at the red side of the first strongabsorption band. The A →T charge-transfer states were predicted to have relativelyhigh energies in the A•T oligonucleotides. The present calculations predict that the T→A charge-transfer states are not involved in the spectra and excited-state dynamics ofthe A•T oligonucleotides. In addition, the influence of base pairing and stacking on thenature of the 1nΠ* and 1ΠΠ* states are discussed in detail.

Keyword
DNA oligonucleotides, DFT, excited states
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-33578 (URN)10.1002/qua.22524 (DOI)000289994300023 ()2-s2.0-79955381712 (ScopusID)
Note
QC 20110520Available from: 2011-05-10 Created: 2011-05-10 Last updated: 2011-05-30Bibliographically approved
2. Nonradiative decay of the lowest excited singlet state of 2-aminopyridine is considerably faster than the radiative decay
Open this publication in new window or tab >>Nonradiative decay of the lowest excited singlet state of 2-aminopyridine is considerably faster than the radiative decay
2009 (English)In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 130, no 14, 144315- p.Article in journal (Refereed) Published
Abstract [en]

Ab initio calculations reveal that radiative lifetime of the lowest excited singlet state of 2-aminopyridine (2AP) molecule should be around 20 ns, consistent with the molecules of the same type, but is about one order of magnitude larger than the claimed experimental fluorescent lifetime in recent years. A S1/S0 conical intersection close to the S1 state has been located which could be the possible nonradiative channel that is responsible for the fast decay observed in the experiment.

Place, publisher, year, edition, pages
America: American -institute of Physics, 2009
Keyword
ab initio calculations, excited states, fluorescences, organic compounds, radiative lifetimes
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:kth:diva-11898 (URN)10.1063/1.3113664 (DOI)000265617200033 ()2-s2.0-65249190165 (ScopusID)
Note
QC20100719 Copyright (2009) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of PhysicsAvailable from: 2010-01-29 Created: 2010-01-21 Last updated: 2011-10-18Bibliographically approved
3. Ultrafast deactivation processes in the 2-aminopyridine dimer and the adenine-thymine base pair: Similarities and differences
Open this publication in new window or tab >>Ultrafast deactivation processes in the 2-aminopyridine dimer and the adenine-thymine base pair: Similarities and differences
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2010 (English)In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 133, no 6, 064302- p.Article in journal (Refereed) Published
Abstract [en]

2-aminopyridine dimer has frequently been used as a model system for studying photochemistry of DNA base pairs. We examine here the relevance of 2-aminopyridine dimer for a Watson-Crick adenine-thymine base pair by studying UV-light induced photodynamics along two main hydrogen bridges after the excitation to the localized (1)pi pi(*) excited-state. The respective two-dimensional potential-energy surfaces have been determined by time-dependent density functional theory with Coulomb-attenuated hybrid exchange-correlation functional (CAM-B3LYP). Different mechanistic aspects of the deactivation pathway have been analyzed and compared in detail for both systems, while the related reaction rates have also be obtained from Monte Carlo kinetic simulations. The limitations of the 2-aminopyridine dimer as a model system for the adenine-thymine base pair are discussed. (C) 2010 American Institute of Physics. [doi:10.1063/1.3464485]

Keyword
density functional theory, DNA, exchange interactions (electron), excited states, Monte Carlo methods, photochemistry, potential energy surfaces, reaction kinetics theory
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:kth:diva-26848 (URN)10.1063/1.3464485 (DOI)000280941800014 ()2-s2.0-77955754884 (ScopusID)
Note
QC 20101202. Updated from submitted to published.Available from: 2010-12-02 Created: 2010-11-29 Last updated: 2012-03-28Bibliographically approved
4. Theoretical Studies on Photoisomerizations of (6-4) and Dewar Photolesions in DNA
Open this publication in new window or tab >>Theoretical Studies on Photoisomerizations of (6-4) and Dewar Photolesions in DNA
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2010 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 114, no 44, 14096-14102 p.Article in journal (Refereed) Published
Abstract [en]

The (6-4) photoproduct ((6-4) PP) is one of the main lesions in UV-induced DNA damage. The (6-4) PP and its valence isomer Dewar photoproduct (Dewar PP) can have a great threat of mutation and cancer but gained much less attention to date. In this study, with density functional theory (DFT) and the complete active space self-consistent field (CASSCF) methods, the photoisomerization processes between the (6-4) PP and the Dewar PP in the gas phase, the aqueous solution, and the photolyase have been carefully examined. Noticeably, the solvent effect is treated with the CASPT2//CASSCF/Amber (QM/MM) method. Our calculations show that the conical intersection (Cl) points play a crucial role in the photoisomerization reaction between the (6-4) PP and the Dewar PP in the gas and the aqueous solution. The ultrafast internal conversion between the S-2 ((1)pi pi*) and the So states via a distorted intersection point is found to be responsible for the formation of the Dewar PP lesion at 313 nm, as observed experimentally. For the reversed isomeric process, two channels involving the "dark" excited states have been identified. In addition to the above passages, in the photolyase, a new electron-injection isomerization process as an efficient way for the photorepair of the Dewar PP is revealed.

Keyword
DEFICIENT HUMAN-CELLS, MOLECULAR-DYNAMICS, CRYSTAL-STRUCTURE, MAMMALIAN-CELLS, REPAIR, PHOTOLYASE, THYMINE, PHOTOPRODUCTS, MECHANISM, PATHWAYS
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-27071 (URN)10.1021/jp107873w (DOI)000283703400022 ()2-s2.0-78149250709 (ScopusID)
Note
QC 20101210Available from: 2010-12-10 Created: 2010-12-06 Last updated: 2011-05-30Bibliographically approved
5. Importance of the Intramolecular Hydrogen Bond on the Photochemistry of Anionic Hydroquinone (FADH-) in DNA Photolyase
Open this publication in new window or tab >>Importance of the Intramolecular Hydrogen Bond on the Photochemistry of Anionic Hydroquinone (FADH-) in DNA Photolyase
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2010 (English)In: Journal of Physical Chemisty Letters, ISSN 1948-7185, Vol. 1, 743-747 p.Article in journal (Refereed) Published
Abstract [en]

The design of a proper molecular model with a good balance between the size of the model system and the computational capacity is essential for theoretical modeling of biological systems. We have shown in this letter that the often used model system, a lumiflavin (7,8-dimethy-10-methyl-isoalloxazine), can not correctly describe geometrical and electronic structures of FADHin DNA photolyase. The intramolecular hydrogen bond between the isoalloxazine ring and the ribityl moiety is found to play a significant role in controlling photochemical properties of FADHin DNA photolyase

Place, publisher, year, edition, pages
U. S. A.: American Chemical Society, 2010
Keyword
flavin, intramolecular hydrogen bonding, excited states
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:kth:diva-11995 (URN)10.1021/jz900434z (DOI)000277040600013 ()2-s2.0-77749242712 (ScopusID)
Funder
Swedish Research Council
Note
QC 20100719Available from: 2010-02-08 Created: 2010-02-08 Last updated: 2012-02-22Bibliographically approved
6. Repair of DNA Dewar Photoproduct to (6-4) photoproduct in (6-4) Photolyase
Open this publication in new window or tab >>Repair of DNA Dewar Photoproduct to (6-4) photoproduct in (6-4) Photolyase
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2011 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, no 37, 10976-10982 p.Article in journal (Refereed) Published
Abstract [en]

Dewar photoproduct (Dewar PP) is the valence isomer of (6-4) photoproduct ((6-4)PP) in photodamaged DNA. Compared to the extensive studied CPD photoproducts, the underlying repair mechanisms for the (6-4)PP, and especially for the Dewar PP, are not well-established to date. In this paper, the repair mechanism of DNA Dewar photoproduct T(dew)C in (6-4) photolyase was elucidated using hybrid density functional theory. Our results showed that, during the repair process, the T(dew)C has to isomerize to T(6-4)C photolesion first via direct C6'-N3' bond cleavage facilitated by electron injection. This isomerization mechanism is energetically much more efficient than other possible rearrangement pathways. The calculations provide a theoretical interpretation to recent experimental observations.

Keyword
DENSITY-FUNCTIONAL THEORY, REACTION-MECHANISM, METHYL INTERMEDIATE, ENZYMATIC-REACTIONS, CRYSTAL-STRUCTURE, ENZYMES, LIGHT, PHOTOLESIONS, HISTIDINES, MOLECULES
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-33526 (URN)10.1021/jp204128k (DOI)000294875100020 ()2-s2.0-80052856745 (ScopusID)
Note
QC 20111010Available from: 2011-05-09 Created: 2011-05-09 Last updated: 2011-10-17Bibliographically approved
7. Intrinsic property of flavin mononucleotide controls its optical spectra in three redox states
Open this publication in new window or tab >>Intrinsic property of flavin mononucleotide controls its optical spectra in three redox states
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2011 (English)In: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 12, no 16, 2899-2902 p.Article in journal (Refereed) Published
Keyword
density functional calculations, flavin mononucleotides, flavodoxins, redox chemistry, vibrational resolved spectroscopy
National Category
Other Physics Topics
Identifiers
urn:nbn:se:kth:diva-33528 (URN)10.1002/cphc.201100663 (DOI)000297017900005 ()2-s2.0-81255147940 (ScopusID)
Note
QC 20111220. Previous title: Intrinsic natural property of flavin mononucleotide controls its optical spectra in three redox statesAvailable from: 2011-05-09 Created: 2011-05-09 Last updated: 2011-12-20Bibliographically approved

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