Finite-Size Effects in Graphene Nanostructures

Finite-Size Effects in Graphene Nanostructure

Large-Scale Quantum Monte Carlo Electronic Structure Calculations on the EGEE Grid

International audienceA grid implementation of a massively parallel quantum Monte Carlo (QMC) code on the EGEE grid architecture is discussed. Technical details allowing an efficient implementation are presented and the grid performance (number of queued, running, and executed tasks as a function of time) is discussed. Finally, we present a very accurate Li2 potential energy curve obtained by running simultaneously several hundreds of tasks on the grid

Photoinduced intersystem crossing in DNA oxidative lesions and epigenetic intermediates

[EN] The propensity of 5-formyluracil and 5-formylcytosine, i.e. oxidative lesions and epigenetic intermediates, in acting as intrinsic DNA photosensitizers is unraveled by using a combination of molecular modeling, simulation and spectroscopy. Exploration of potential energy surfaces and non-adiabatic dynamics confirm a higher intersystem crossing rate for 5-formyluracil, whereas the kinetic models evidence different equilibria in the excited states for both compounds.Support from the Universite de Lorraine, CNRS and Spanish Government (PGC2018-096684-B-I00) is kindly acknowledged. A. F.-M. is grateful to Generalitat Valenciana (CTQ2017-87054-C2-2-P) and the European Social Fund for a postdoctoral contract (APOSTD/2019/149), M. L.-R. acknowledges the Universitat Politecnica de Valencia for the FPI grant. Calculations have been performed on the local LPCT computer center and on the Explor regional center in the framework of the project "Dancing under the light''.Francés-Monerris, A.; Lineros-Rosa, M.; Miranda Alonso, MÁ.; Lhiaubet, VL.; Monari, A. (2020). Photoinduced intersystem crossing in DNA oxidative lesions and epigenetic intermediates. Chemical Communications. 56(32):4404-4407. https://doi.org/10.1039/d0cc01132kS440444075632Madabhushi, R., Pan, L., & Tsai, L.-H. (2014). DNA Damage and Its Links to Neurodegeneration. Neuron, 83(2), 266-282. doi:10.1016/j.neuron.2014.06.034Sage, E. (1993). DISTRIBUTION AND REPAIR OF PHOTOLESIONS IN DNA: GENETIC CONSEQUENCES AND THE ROLE OF SEQUENCE CONTEXT. Photochemistry and Photobiology, 57(1), 163-174. doi:10.1111/j.1751-1097.1993.tb02273.xCadet, J., Sage, E., & Douki, T. (2005). Ultraviolet radiation-mediated damage to cellular DNA. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 571(1-2), 3-17. doi:10.1016/j.mrfmmm.2004.09.012G. T. Wondrak , Skin stress response pathways: Environmental factors and molecular opportunities , Springer , 2016Nakamura, J., Mutlu, E., Sharma, V., Collins, L., Bodnar, W., Yu, R., … Swenberg, J. (2014). The endogenous exposome. DNA Repair, 19, 3-13. doi:10.1016/j.dnarep.2014.03.031Esposito, L., Banyasz, A., Douki, T., Perron, M., Markovitsi, D., & Improta, R. (2014). Effect of C5-Methylation of Cytosine on the Photoreactivity of DNA: A Joint Experimental and Computational Study of TCG Trinucleotides. Journal of the American Chemical Society, 136(31), 10838-10841. doi:10.1021/ja5040478Ikehata, H., Mori, T., Kamei, Y., Douki, T., Cadet, J., & Yamamoto, M. (2019). Wavelength‐ and Tissue‐dependent Variations in the Mutagenicity of Cyclobutane Pyrimidine Dimers in Mouse Skin. Photochemistry and Photobiology, 96(1), 94-104. doi:10.1111/php.13159Cadet, J., & Douki, T. (2018). Formation of UV-induced DNA damage contributing to skin cancer development. Photochemical & Photobiological Sciences, 17(12), 1816-1841. doi:10.1039/c7pp00395aDumont, E., & Monari, A. (2015). Understanding DNA under oxidative stress and sensitization: the role of molecular modeling. Frontiers in Chemistry, 3. doi:10.3389/fchem.2015.00043Cadet, J., & Wagner, J. R. (2013). DNA Base Damage by Reactive Oxygen Species, Oxidizing Agents, and UV Radiation. Cold Spring Harbor Perspectives in Biology, 5(2), a012559-a012559. doi:10.1101/cshperspect.a012559Banyasz, A., Douki, T., Improta, R., Gustavsson, T., Onidas, D., Vayá, I., … Markovitsi, D. (2012). Electronic Excited States Responsible for Dimer Formation upon UV Absorption Directly by Thymine Strands: Joint Experimental and Theoretical Study. Journal of the American Chemical Society, 134(36), 14834-14845. doi:10.1021/ja304069fRauer, C., Nogueira, J. J., Marquetand, P., & González, L. (2016). Cyclobutane Thymine Photodimerization Mechanism Revealed by Nonadiabatic Molecular Dynamics. Journal of the American Chemical Society, 138(49), 15911-15916. doi:10.1021/jacs.6b06701IKEHATA, H., & ONO, T. (2011). The Mechanisms of UV Mutagenesis. Journal of Radiation Research, 52(2), 115-125. doi:10.1269/jrr.10175Gomez-Mendoza, M., Banyasz, A., Douki, T., Markovitsi, D., & Ravanat, J.-L. (2016). Direct Oxidative Damage of Naked DNA Generated upon Absorption of UV Radiation by Nucleobases. The Journal of Physical Chemistry Letters, 7(19), 3945-3948. doi:10.1021/acs.jpclett.6b01781Banyasz, A., Martínez-Fernández, L., Balty, C., Perron, M., Douki, T., Improta, R., & Markovitsi, D. (2017). Absorption of Low-Energy UV Radiation by Human Telomere G-Quadruplexes Generates Long-Lived Guanine Radical Cations. Journal of the American Chemical Society, 139(30), 10561-10568. doi:10.1021/jacs.7b05931Epe, B. (2012). DNA damage spectra induced by photosensitization. Photochem. Photobiol. Sci., 11(1), 98-106. doi:10.1039/c1pp05190cCuquerella, M. C., Lhiaubet-Vallet, V., Cadet, J., & Miranda, M. A. (2012). Benzophenone Photosensitized DNA Damage. Accounts of Chemical Research, 45(9), 1558-1570. doi:10.1021/ar300054eCuquerella, M. C., Lhiaubet-Vallet, V., Bosca, F., & Miranda, M. A. (2011). Photosensitised pyrimidine dimerisation in DNA. Chemical Science, 2(7), 1219. doi:10.1039/c1sc00088hV. Lhiaubet-Vallet and M. A.Miranda , in CRC handbook of organic photochemistry and photobiology , ed. F. Ghetti , A. G. Griesbeck and M. Oelgemöller , CRC Press , 2012 , pp. 1541–1555Cadet, J., Douki, T., & Ravanat, J.-L. (2008). Oxidatively Generated Damage to the Guanine Moiety of DNA: Mechanistic Aspects and Formation in Cells. Accounts of Chemical Research, 41(8), 1075-1083. doi:10.1021/ar700245eDumont, E., Grüber, R., Bignon, E., Morell, C., Moreau, Y., Monari, A., & Ravanat, J.-L. (2015). Probing the reactivity of singlet oxygen with purines. Nucleic Acids Research, 44(1), 56-62. doi:10.1093/nar/gkv1364Baptista, M. S., Cadet, J., Di Mascio, P., Ghogare, A. A., Greer, A., Hamblin, M. R., … Yoshimura, T. M. (2017). Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways. Photochemistry and Photobiology, 93(4), 912-919. doi:10.1111/php.12716Dumont, E., Wibowo, M., Roca-Sanjuán, D., Garavelli, M., Assfeld, X., & Monari, A. (2015). Resolving the Benzophenone DNA-Photosensitization Mechanism at QM/MM Level. The Journal of Physical Chemistry Letters, 6(4), 576-580. doi:10.1021/jz502562dDumont, É., & Monari, A. (2014). Interaction of Palmatine with DNA: An Environmentally Controlled Phototherapy Drug. The Journal of Physical Chemistry B, 119(2), 410-419. doi:10.1021/jp5088515Nogueira, J. J., Oppel, M., & González, L. (2015). Enhancing Intersystem Crossing in Phenotiazinium Dyes by Intercalation into DNA. Angewandte Chemie International Edition, 54(14), 4375-4378. doi:10.1002/anie.201411456Vendrell-Criado, V., Rodríguez-Muñiz, G. M., Cuquerella, M. C., Lhiaubet-Vallet, V., & Miranda, M. A. (2013). Photosensitization of DNA by 5-Methyl-2-Pyrimidone Deoxyribonucleoside: (6-4) Photoproduct as a Possible Trojan Horse. Angewandte Chemie International Edition, 52(25), 6476-6479. doi:10.1002/anie.201302176Vendrell-Criado, V., Rodríguez-Muñiz, G. M., Lhiaubet-Vallet, V., Cuquerella, M. C., & Miranda, M. A. (2016). The (6-4) Dimeric Lesion as a DNA Photosensitizer. ChemPhysChem, 17(13), 1979-1982. doi:10.1002/cphc.201600154Bignon, E., Gattuso, H., Morell, C., Dumont, E., & Monari, A. (2015). DNA Photosensitization by an «Insider»: Photophysics and Triplet Energy Transfer of 5‐Methyl‐2‐pyrimidone Deoxyribonucleoside. Chemistry – A European Journal, 21(32), 11509-11516. doi:10.1002/chem.201501212Francés-Monerris, A., Hognon, C., Miranda, M. A., Lhiaubet-Vallet, V., & Monari, A. (2018). Triplet photosensitization mechanism of thymine by an oxidized nucleobase: from a dimeric model to DNA environment. Physical Chemistry Chemical Physics, 20(40), 25666-25675. doi:10.1039/c8cp04866eLiu, P., Burdzy, A., & Sowers, L. C. (2003). Repair of the mutagenic DNA oxidation product, 5-formyluracil. DNA Repair, 2(2), 199-210. doi:10.1016/s1568-7864(02)00198-2Rogstad, D. K., Heo, J., Vaidehi, N., Goddard, W. A., Burdzy, A., & Sowers, L. C. (2004). 5-Formyluracil-Induced Perturbations of DNA Function. Biochemistry, 43(19), 5688-5697. doi:10.1021/bi030247jWang, Y., Zhang, X., Zou, G., Peng, S., Liu, C., & Zhou, X. (2019). Detection and Application of 5-Formylcytosine and 5-Formyluracil in DNA. Accounts of Chemical Research, 52(4), 1016-1024. doi:10.1021/acs.accounts.8b00543Xing, J., Ai, Y., Liu, Y., Du, J., Chen, W., Lu, Z., & Wang, X. (2018). Theoretical Studies on the Photophysics and Photochemistry of 5-Formylcytosine and 5-Carboxylcytosine: The Oxidative Products of Epigenetic Modification of Cytosine in DNA. The Journal of Physical Chemistry B, 122(10), 2704-2714. doi:10.1021/acs.jpcb.7b10218López, V., Fernández, A. F., & Fraga, M. F. (2017). The role of 5-hydroxymethylcytosine in development, aging and age-related diseases. Ageing Research Reviews, 37, 28-38. doi:10.1016/j.arr.2017.05.002Berson, A., Nativio, R., Berger, S. L., & Bonini, N. M. (2018). Epigenetic Regulation in Neurodegenerative Diseases. Trends in Neurosciences, 41(9), 587-598. doi:10.1016/j.tins.2018.05.005Deans, C., & Maggert, K. A. (2015). What Do You Mean, «Epigenetic»? Genetics, 199(4), 887-896. doi:10.1534/genetics.114.173492Hognon, C., Besancenot, V., Gruez, A., Grandemange, S., & Monari, A. (2019). Cooperative Effects of Cytosine Methylation on DNA Structure and Dynamics. The Journal of Physical Chemistry B, 123(34), 7365-7371. doi:10.1021/acs.jpcb.9b05835Tang, Y., Zheng, S.-J., Qi, C.-B., Feng, Y.-Q., & Yuan, B.-F. (2015). Sensitive and Simultaneous Determination of 5-Methylcytosine and Its Oxidation Products in Genomic DNA by Chemical Derivatization Coupled with Liquid Chromatography-Tandem Mass Spectrometry Analysis. Analytical Chemistry, 87(6), 3445-3452. doi:10.1021/ac504786rBachman, M., Uribe-Lewis, S., Yang, X., Burgess, H. E., Iurlaro, M., Reik, W., … Balasubramanian, S. (2015). 5-Formylcytosine can be a stable DNA modification in mammals. Nature Chemical Biology, 11(8), 555-557. doi:10.1038/nchembio.1848Iurlaro, M., Ficz, G., Oxley, D., Raiber, E.-A., Bachman, M., Booth, M. J., … Reik, W. (2013). A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation. Genome Biology, 14(10), R119. doi:10.1186/gb-2013-14-10-r119Etienne, T., Assfeld, X., & Monari, A. (2014). Toward a Quantitative Assessment of Electronic Transitions’ Charge-Transfer Character. Journal of Chemical Theory and Computation, 10(9), 3896-3905. doi:10.1021/ct5003994Crespo-Otero, R., & Barbatti, M. (2018). Recent Advances and Perspectives on Nonadiabatic Mixed Quantum–Classical Dynamics. Chemical Reviews, 118(15), 7026-7068. doi:10.1021/acs.chemrev.7b00577Mai, S., Marquetand, P., & González, L. (2015). A general method to describe intersystem crossing dynamics in trajectory surface hopping. International Journal of Quantum Chemistry, 115(18), 1215-1231. doi:10.1002/qua.24891Martin, R. L. (2003). Natural transition orbitals. The Journal of Chemical Physics, 118(11), 4775-4777. doi:10.1063/1.1558471Janicki, M. J., Szabla, R., Šponer, J., & Góra, R. W. (2018). Solvation effects alter the photochemistry of 2-thiocytosine. Chemical Physics, 515, 502-508. doi:10.1016/j.chemphys.2018.06.016Mai, S., Pollum, M., Martínez-Fernández, L., Dunn, N., Marquetand, P., Corral, I., … González, L. (2016). The origin of efficient triplet state population in sulfur-substituted nucleobases. Nature Communications, 7(1). doi:10.1038/ncomms13077Marazzi, M., Mai, S., Roca-Sanjuán, D., Delcey, M. G., Lindh, R., González, L., & Monari, A. (2016). Benzophenone Ultrafast Triplet Population: Revisiting the Kinetic Model by Surface-Hopping Dynamics. The Journal of Physical Chemistry Letters, 7(4), 622-626. doi:10.1021/acs.jpclett.5b0279

A theoretical study of linear beryllium chains: full configuration interaction.

International audienceWe present a full configuration interaction study of Be(N) (N=2,3,4,5) linear chains. A comparative study of the basis-set effect on the reproduction of the energy profile has been reported. In particular, the 3s1p, 4s2p, 4s2p1d, 5s3p2d, and 5s3p2d1f bases were selected. For the smallest chains (i.e., Be(2) and Be(3)), smaller basis sets give dissociative energy profiles, so large basis set is demanded for the reproduction of equilibrium minima in the structures. For Be(4) and Be(5) linear chains, the energy profiles show a minimum also by using the smallest basis sets, but the largest ones give a much stronger stabilization energy. For all the structures, two spin states have been studied: the singlet and the triplet. It is shown that the energy separation of the two states, in the equilibrium region, is small and decays exponentially with respect to the number of atoms in the chain. Finally an interpolative technique allowing for the estimation of the long-chain parameters from shorter ones is presented

Experimental and theoretical studies on thymine photodimerization mediated by oxidatively generated DNA lesions and epigenetic intermediates

[EN] Interaction of nucleic acids with light is a scientific question of paramount relevance not only in the understanding of life functioning and evolution, but also in the insurgence of diseases such as malignant skin cancer and in the development of biomarkers and novel light-assisted therapeutic tools. This work shows that the UVA portion of sunlight, not absorbed by canonical DNA nucleobases, can be absorbed by 5-formyluracil (ForU) and 5-formylcytosine (ForC), two ubiquitous oxidatively generated lesions and epigenetic intermediates present in living beings in natural conditions. We measure the strong propensity of these molecules to populate triplet excited states able to transfer the excitation energy to thymine-thymine dyads, inducing the formation of cyclobutane pyrimidine dimers (CPDs). By using steady-state and transient absorption spectroscopy, NMR, HPLC, and theoretical calculations, we quantify the differences in the triplet-triplet energy transfer mediated by ForU and ForC, revealing that the former is much more efficient in delivering the excitation energy and producing the CPD photoproduct. Although significantly slower than ForU, ForC is also able to harm DNA nucleobases and therefore this process has to be taken into account as a viable photosensitization mechanism. The present findings evidence a rich photochemistry crucial to understand DNA damage photobehavior.Support from the Universite de Lorraine, CNRS, regional (Prometeo/2017/075) and Spanish Government (PGC2018-096684-B-I00, CTQ2017-87054-C2-2-P) is kindly acknowledged. A. F.-M. is grateful to Generalitat Valenciana and the European Social Fund (postdoctoral contract APOSTD/2019/149 and project GV/2020/226) for financial support. M. L.-R. acknowledges the Universitat Politecnica de Valencia for the FPI grant. All calculations have been performed on the local LPCT computer center and on the Explor regional center in the framework of the project "Dancing under the light".Lineros-Rosa, M.; Francés-Monerris, A.; Monari, A.; Miranda Alonso, MÁ.; Lhiaubet, VL. (2020). Experimental and theoretical studies on thymine photodimerization mediated by oxidatively generated DNA lesions and epigenetic intermediates. Physical Chemistry Chemical Physics. 22(44):25661-25668. https://doi.org/10.1039/d0cp04557hS25661256682244Crespo-Hernández, C. E., Cohen, B., Hare, P. M., & Kohler, B. (2004). Ultrafast Excited-State Dynamics in Nucleic Acids. Chemical Reviews, 104(4), 1977-2020. doi:10.1021/cr0206770Improta, R., Santoro, F., & Blancafort, L. (2016). Quantum Mechanical Studies on the Photophysics and the Photochemistry of Nucleic Acids and Nucleobases. Chemical Reviews, 116(6), 3540-3593. doi:10.1021/acs.chemrev.5b00444Sage, E., Girard, P.-M., & Francesconi, S. (2012). Unravelling UVA-induced mutagenesis. Photochem. Photobiol. Sci., 11(1), 74-80. doi:10.1039/c1pp05219eFrancés-Monerris, A., Gattuso, H., Roca-Sanjuán, D., Tuñón, I., Marazzi, M., Dumont, E., & Monari, A. (2018). Dynamics of the excited-state hydrogen transfer in a (dG)·(dC) homopolymer: intrinsic photostability of DNA. Chemical Science, 9(41), 7902-7911. doi:10.1039/c8sc03252aZhang, Y., de La Harpe, K., Beckstead, A. A., Improta, R., & Kohler, B. (2015). UV-Induced Proton Transfer between DNA Strands. Journal of the American Chemical Society, 137(22), 7059-7062. doi:10.1021/jacs.5b03914Zhang, Y., Li, X.-B., Fleming, A. M., Dood, J., Beckstead, A. A., Orendt, A. M., … Kohler, B. (2016). UV-Induced Proton-Coupled Electron Transfer in Cyclic DNA Miniduplexes. Journal of the American Chemical Society, 138(23), 7395-7401. doi:10.1021/jacs.6b03216Bucher, D. B., Schlueter, A., Carell, T., & Zinth, W. (2014). Watson-Crick Base Pairing Controls Excited-State Decay in Natural DNA. Angewandte Chemie International Edition, 53(42), 11366-11369. doi:10.1002/anie.201406286Röttger, K., Marroux, H. J. B., Grubb, M. P., Coulter, P. M., Böhnke, H., Henderson, A. S., … Roberts, G. M. (2015). Ultraviolet Absorption Induces Hydrogen‐Atom Transfer in G⋅C Watson–Crick DNA Base Pairs in Solution. Angewandte Chemie International Edition, 54(49), 14719-14722. doi:10.1002/anie.201506940Nogueira, J. J., Plasser, F., & González, L. (2017). Electronic delocalization, charge transfer and hypochromism in the UV absorption spectrum of polyadenine unravelled by multiscale computations and quantitative wavefunction analysis. Chemical Science, 8(8), 5682-5691. doi:10.1039/c7sc01600jBarbatti, M., Aquino, A. J. A., Szymczak, J. J., Nachtigallova, D., Hobza, P., & Lischka, H. (2010). Relaxation mechanisms of UV-photoexcited DNA and RNA nucleobases. Proceedings of the National Academy of Sciences, 107(50), 21453-21458. doi:10.1073/pnas.1014982107Reiter, S., Keefer, D., & de Vivie-Riedle, R. (2018). RNA Environment Is Responsible for Decreased Photostability of Uracil. Journal of the American Chemical Society, 140(28), 8714-8720. doi:10.1021/jacs.8b02962Cuquerella, M. C., Lhiaubet-Vallet, V., Bosca, F., & Miranda, M. A. (2011). Photosensitised pyrimidine dimerisation in DNA. Chemical Science, 2(7), 1219. doi:10.1039/c1sc00088hMouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2006). Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proceedings of the National Academy of Sciences, 103(37), 13765-13770. doi:10.1073/pnas.0604213103Ikehata, H., Mori, T., Kamei, Y., Douki, T., Cadet, J., & Yamamoto, M. (2019). Wavelength‐ and Tissue‐dependent Variations in the Mutagenicity of Cyclobutane Pyrimidine Dimers in Mouse Skin. Photochemistry and Photobiology, 96(1), 94-104. doi:10.1111/php.13159Pfeifer, G. P., & Besaratinia, A. (2012). UV wavelength-dependent DNA damage and human non-melanoma and melanoma skin cancer. Photochem. Photobiol. Sci., 11(1), 90-97. doi:10.1039/c1pp05144jNoonan, F. P., Zaidi, M. R., Wolnicka-Glubisz, A., Anver, M. R., Bahn, J., Wielgus, A., … De Fabo, E. C. (2012). Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment. Nature Communications, 3(1). doi:10.1038/ncomms1893Sinha, R. P., & Häder, D.-P. (2002). UV-induced DNA damage and repair: a review. Photochemical & Photobiological Sciences, 1(4), 225-236. doi:10.1039/b201230hMouret, S., Philippe, C., Gracia-Chantegrel, J., Banyasz, A., Karpati, S., Markovitsi, D., & Douki, T. (2010). UVA-induced cyclobutane pyrimidine dimers in DNA: a direct photochemical mechanism? Organic & Biomolecular Chemistry, 8(7), 1706. doi:10.1039/b924712bEpe, B. (2012). DNA damage spectra induced by photosensitization. Photochem. Photobiol. Sci., 11(1), 98-106. doi:10.1039/c1pp05190cCadet, J., & Douki, T. (2018). Formation of UV-induced DNA damage contributing to skin cancer development. Photochemical & Photobiological Sciences, 17(12), 1816-1841. doi:10.1039/c7pp00395aFrancés-Monerris, A., Tuñón, I., & Monari, A. (2019). Hypoxia-Selective Dissociation Mechanism of a Nitroimidazole Nucleoside in a DNA Environment. The Journal of Physical Chemistry Letters, 10(21), 6750-6754. doi:10.1021/acs.jpclett.9b02760Roca-Sanjuán, D., Olaso-González, G., González-Ramírez, I., Serrano-Andrés, L., & Merchán, M. (2008). Molecular Basis of DNA Photodimerization: Intrinsic Production of Cyclobutane Cytosine Dimers. Journal of the American Chemical Society, 130(32), 10768-10779. doi:10.1021/ja803068nCliment, T., González-Ramírez, I., González-Luque, R., Merchán, M., & Serrano-Andrés, L. (2010). Cyclobutane Pyrimidine Photodimerization of DNA/RNA Nucleobases in the Triplet State. The Journal of Physical Chemistry Letters, 1(14), 2072-2076. doi:10.1021/jz100601pDumont, E., & Monari, A. (2015). Understanding DNA under oxidative stress and sensitization: the role of molecular modeling. Frontiers in Chemistry, 3. doi:10.3389/fchem.2015.00043Lhiaubet-Vallet, V., Sarabia, Z., Hernández, D., Castell, J. ., & Miranda, M. . (2003). In vitro studies on DNA-photosensitization by different drug stereoisomers. Toxicology in Vitro, 17(5-6), 651-656. doi:10.1016/s0887-2333(03)00108-5Sauvaigo, S., Douki, T., Odin, F., Caillat, S., Ravanat, J.-L., & Cadet, J. (2001). Analysis of Fluoroquinolone-mediated Photosensitization of 2′-Deoxyguanosine, Calf Thymus and Cellular DNA: Determination of Type-I, Type-II and Triplet–Triplet Energy Transfer Mechanism Contribution¶. Photochemistry and Photobiology, 73(3), 230. doi:10.1562/0031-8655(2001)0732.0.co;2Lhiaubet-Vallet, V., Bosca, F., & Miranda, M. A. (2009). Photosensitized DNA Damage: The Case of Fluoroquinolones. Photochemistry and Photobiology, 85(4), 861-868. doi:10.1111/j.1751-1097.2009.00548.xCuquerella, M. C., Lhiaubet-Vallet, V., Cadet, J., & Miranda, M. A. (2012). Benzophenone Photosensitized DNA Damage. Accounts of Chemical Research, 45(9), 1558-1570. doi:10.1021/ar300054eMarazzi, M., Mai, S., Roca-Sanjuán, D., Delcey, M. G., Lindh, R., González, L., & Monari, A. (2016). Benzophenone Ultrafast Triplet Population: Revisiting the Kinetic Model by Surface-Hopping Dynamics. The Journal of Physical Chemistry Letters, 7(4), 622-626. doi:10.1021/acs.jpclett.5b02792Dumont, E., Wibowo, M., Roca-Sanjuán, D., Garavelli, M., Assfeld, X., & Monari, A. (2015). Resolving the Benzophenone DNA-Photosensitization Mechanism at QM/MM Level. The Journal of Physical Chemistry Letters, 6(4), 576-580. doi:10.1021/jz502562dVendrell-Criado, V., Rodríguez-Muñiz, G. M., Cuquerella, M. C., Lhiaubet-Vallet, V., & Miranda, M. A. (2013). Photosensitization of DNA by 5-Methyl-2-Pyrimidone Deoxyribonucleoside: (6-4) Photoproduct as a Possible Trojan Horse. Angewandte Chemie International Edition, 52(25), 6476-6479. doi:10.1002/anie.201302176Bignon, E., Gattuso, H., Morell, C., Dumont, E., & Monari, A. (2015). DNA Photosensitization by an «Insider»: Photophysics and Triplet Energy Transfer of 5‐Methyl‐2‐pyrimidone Deoxyribonucleoside. Chemistry – A European Journal, 21(32), 11509-11516. doi:10.1002/chem.201501212Rogstad, D. K., Heo, J., Vaidehi, N., Goddard, W. A., Burdzy, A., & Sowers, L. C. (2004). 5-Formyluracil-Induced Perturbations of DNA Function. Biochemistry, 43(19), 5688-5697. doi:10.1021/bi030247jBachman, M., Uribe-Lewis, S., Yang, X., Burgess, H. E., Iurlaro, M., Reik, W., … Balasubramanian, S. (2015). 5-Formylcytosine can be a stable DNA modification in mammals. Nature Chemical Biology, 11(8), 555-557. doi:10.1038/nchembio.1848Wang, Y., Zhang, X., Zou, G., Peng, S., Liu, C., & Zhou, X. (2019). 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Novel Molecular-Dynamics-Based Protocols for Phase Space Sampling in Complex Systems

The adequate exploration of the phase space of a chromophore is a fundamental necessity for the simulation of their optical and photophysical properties, taking into account the effects of vibrational motion and, most importantly, the coupling with a (non-homogeneous) molecular environment. A representative set of conformational snapshots around the Franck-Condon region is also required to perform non-adiabatic molecular dynamics, for instance in the framework of surface hopping. Indeed, in the latter case one needs to prepare a set of initial conditions providing a meaningful and complete statistical base for the subsequent trajectory propagation. In this contribution, we propose two new protocols for molecular dynamics-based phase space sampling, called “local temperature adjustment” and “individual QM/MM-based relaxation.” These protocols are intended for situations in which the popular Wigner distribution sampling procedure is not applicable—as it is the case when anharmonic or nonlinear vibrations are present—and where regular molecular dynamics sampling might suffer from an inaccurate distribution of internal energy or from inaccurate force fields. The new protocols are applied to the case of phase space sampling of [Re(CO)3(Im)(Phen)]+ (im, imidazole; phen, phenanthroline) in aqueous solution, showing the advantages and limitations of regular Wigner and molecular dynamics sampling as well as the strengths of the new protocols

Competing ultrafast photoinduced electron transfer and intersystem crossing of [Re(CO)(3)(Dmp)(His124)(Trp122)]+ in Pseudomonas aeruginosa azurin:a nonadiabatic dynamics study

We present a computational study of sub-picosecond nonadiabatic dynamics in a rhenium complex coupled electronically to a tryptophan (Trp) side chain of Pseudomonas aeruginosa azurin, a prototypical protein used in the study of electron transfer in proteins. To gain a comprehensive understanding of the photoinduced processes in this system, we have carried out vertical excitation calculations at the TDDFT level of theory as well as nonadiabatic dynamics simulations using the surface hopping including arbitrary couplings (SHARC) method coupled to potential energy surfaces represented with a linear vibronic coupling model. The results show that the initial photoexcitation populates both singlet metal-to-ligand charge transfer (MLCT) and singlet charge-separated (CS) states, where in the latter an electron was transferred from the Trp amino acid to the complex. Subsequently, a complex mechanism of simultaneous intersystem crossing and electron transfer leads to the sub-picosecond population of triplet MLCT and triplet CS states. These results confirm the assignment of the sub-ps time constants of previous experimental studies and constitute the first computational evidence for the ultrafast formation of the charge-separated states in Re-sensitized azurin

Understanding the Interactions of Guanine Quadruplexes with Peptides as Novel Strategies for Diagnosis or Tuning Biological Functions

Guanine quadruplexes (G4s) are nucleic acid structures exhibiting a complex structural behavior and exerting crucial biological functions in both cells and viruses. The specific interactions of peptides with G4s, as well as an understanding of the factors driving the specific recognition are important for the rational design of both therapeutic and diagnostic agents. In this review, we examine the most important studies dealing with the interactions between G4s and peptides, highlighting the strengths and limitations of current analytic approaches. We also show how the combined use of high-level molecular simulation techniques and experimental spectroscopy is the best avenue to design specifically tuned and selective peptides, thus leading to the control of important biological functions

Thermodynamics of the interaction between spike protein of severe acute respiratory syndrome-coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 1000000 deaths all over the world and still lacks a medical treatment despite the attention of the whole scientific community. Human angiotensin-converting enzyme 2 (ACE2) was recently recognized as the transmembrane protein that serves as the point of entry of SARS-CoV-2 into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the protein complex. Moreover, the free energy of binding between ACE2 and the active receptor binding domain of the SARS-CoV-2 spike protein is evaluated quantitatively, providing for the first time the thermodynamics of virus?receptor recognition. Furthermore, the action of different ACE2 ligands is also examined in particular in their capacity to disrupt SARS-CoV-2 recognition, also providing via a free energy profile the quantification of the ligand-induced decreased affinity. These results improve our knowledge on molecular grounds of the SARS-CoV-2 infection and allow us to suggest rationales that could be useful for the subsequent wise molecular design for the treatment of COVID-19 cases

Excited-states of a rhenium carbonyl diimine complex: solvation models, spin-orbit coupling, and vibrational sampling effects

Presentamos una investigación química cuántica de los estados excitados del complejo [Re (CO) 3 (Im) (Phen)] + (Im = imidazol; Phen = 1,10-fenantrolina) en solución que incluye acoplamientos de giro-órbita y muestreo vibracional. Para este objetivo, implementamos la mecánica cuántica / mecánica molecular (QM / MM) de incrustación electrostática en el conjunto de programas funcionales de densidad de Ámsterdam, adecuados para cálculos funcionales de densidad dependientes del tiempo que incluyen acoplamientos de órbita de espín. La nueva implementación se emplea para simular el espectro de absorción del complejo, que se compara con los resultados de la solvatación continua implícita y la inclusión de densidad congelada. Se utilizan simulaciones de dinámica molecular para muestrear las conformaciones del estado fundamental en la solución. Los resultados demuestran que cualquier estudio de los estados excitados de [Re (CO) 3 (Im) (Phen)] + en solución y su dinámica debe incluir un muestreo extenso de movimiento vibracional y acoplamientos de giro-órbita.We present a quantum-chemical investigation of the excited states of the complex [Re(CO)3(Im)(Phen)]+ (Im = imidazole; Phen = 1,10-phenanthroline) in solution including spin–orbit couplings and vibrational sampling. To this aim, we implemented electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) in the Amsterdam Density Functional program suite, suitable for time-dependent density functional calculations including spin–orbit couplings. The new implementation is employed to simulate the absorption spectrum of the complex, which is compared to the results of implicit continuum solvation and frozen-density embedding. Molecular dynamics simulations are used to sample the ground state conformations in solution. The results demonstrate that any study of the excited states of [Re(CO)3(Im)(Phen)]+ in solution and their dynamics should include extensive sampling of vibrational motion and spin–orbit couplings.• Austrian Science Fund. Proyecto I2883, para Sebastian Mai, Aurora Muñoz-Losa, Letizia González Herrero • Agence Nationale de la Recherche (ANR). Proyecto ANR-15-CE29-0027, para Hugo Gattuso, Maria Fumanal, Antonio Monari, Chantal Daniel • Financial Reporting Council y Labex CSC. Proyecto ANR-10-LABX-0026_CSC, para Maria Fumanal, Chantal Daniel • Action CM1405 - COSTpeerReviewe