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Photochemistry of Thymine in Solution and DNA Revealed by an Electrostatic Embedding QM/MM Combined with Mixed-Reference Spin-Flip TDDFT

Huix-Rotllant, Miquel and Schwinn, Karno and Pomogaev, Vladimir and Farmani, Maryam and Ferré, Nicolas and Lee, Seunghoon and Choi, Cheol Ho (2023) Photochemistry of Thymine in Solution and DNA Revealed by an Electrostatic Embedding QM/MM Combined with Mixed-Reference Spin-Flip TDDFT. Journal of Chemical Theory and Computation, 19 (1). pp. 147-156. ISSN 1549-9618. doi:10.1021/acs.jctc.2c01010.

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The photochemistry of nucleobases, important for their role as building blocks of DNA, is largely affected by the electrostatic environment in which they are soaked. For example, despite the numerous studies of thymine in solution and DNA, there is still a debate on the photochemical deactivation pathways after UV absorption. Many theoretical models are oversimplified due to the lack of computationally accurate and efficient electronic structure methodologies that capture excited state electron correlation effects when nucleobases are embedded in large electrostatic media. Here, we combine mixed-reference spin-flip time-dependent density functional theory (MRSF-TDDFT) with electrostatic embedding QM/MM using electrostatic potential fittingfitted (ESPF) atomic charges, as a strategy to accurately and efficiently describe the electronic structure of chromophores polarized by an electrostatic medium. In particular, we develop analytic expressions for the energy and gradient of MRSF/MM based on the ESPF coupling using atom-centered grids and total charge conservation. We apply this methodology to the study of solvation effects on thymine photochemistry in water and thymine dimers in DNA. In the former, the combination of trajectory surface hopping (TSH) nonadiabatic molecular dynamics (NAMD) with MRSF/MM remarkably revealed accelerated deactivation decay pathways, which is consistent with the experimental decay time of ∼400 fs. The enhanced hopping rate can be explained by the preferential stabilization of corresponding conical interactions due to their increased dipole moments. Structurally, it is a consequence of characteristic methyl puckered geometries near the conical intersection region. For the thymine dimer in B-DNA, we found new photochemical pathways through conical intersections that could explain the formation of cyclobutadiene dimers and 6–4 photoproducts.

Item Type:Article
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URLURL TypeDescription
Huix-Rotllant, Miquel0000-0002-2131-7328
Pomogaev, Vladimir0000-0003-4774-3998
Ferré, Nicolas0000-0002-5583-8834
Lee, Seunghoon0000-0003-3665-587X
Choi, Cheol Ho0000-0002-8757-1396
Additional Information:M.H.R. and K.S. acknowledge financial support by the “Agence Nationale pour la Recherche” through the project BIOMAGNET (ANR-16-CE29-0008-01). Centre de Calcul Intensif d’Aix-Marseille is acknowledged for granting access to its high performance computing resources. All authors are thankful for the financing through the program PHC STAR 2019 granted by the “ministère de l’Europe et des Affaires étrangères” (MEAE), the “ministère de l’Enseignement supérieur, de la Recherche et de l’Innovation” (MESRI), and the National Research Foundation of Korea (NRF). This work was supported by the Samsung Science and Technology Foundations (SSTF-BA1701-12) for the fundamental theory developments and the NRF funded by the Ministry of Science and ICT (2020R1A2C2008246 and 2020R1A5A1019141).
Funding AgencyGrant Number
Agence Nationale pour la Recherche (ANR)ANR-16-CE29-0008-01
Samsung Science and Technology FoundationBA1701-12
Ministry of Science and ICT (Korea)2020R1A2C2008246
Ministry of Science and ICT (Korea)2020R1A5A1019141
Issue or Number:1
Record Number:CaltechAUTHORS:20230123-451841300.44
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:118905
Deposited By: Research Services Depository
Deposited On:24 Feb 2023 18:03
Last Modified:24 Feb 2023 18:03

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