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Radical cation transfer in a guanine pair: an insight to the G-quadruplex structure role using constrained DFT/MM

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Abstract

DNA G-Quadruplex is highly sensitive to oxidation as their structures include \(\pi\)-stacked guanine quartets allowing fast hole transfer between the nucleobases. These transfers can be described using vertical energy gap and electronic coupling between the different diabatic states at play in a guanine pair. Using classical molecular dynamics simulation and the constrained DFT/MM implementation in deMon2k, we determine these quantities for all the interacting guanine pairs of six G-quadruplex structures including one to four quartets and corresponding to different DNA folding. We then described an uni-directional transfer within a quartet, with high electronic coupling and vertical energy gap values, which contrasts with the hole transfer between \(\pi\)-stacked guanine, bi-directional and corresponding to smaller charge transfer parameters. The influence of the geometrical parameters on the electronic coupling is explored, while the external or internal position of the guanine may impact its oxidation probability according to the vertical energy gaps.

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Acknowledgements

R.R. is grateful for the IISER-ENS de Lyon fellowship which has financed her visit at the ENS de Lyon. The authors thank the SYSPROD Project and AXELERA Pôle de Compétitivité for financial support (PSMN Data Center). This work was performed using HPC resources from GENCI-IDRIS (Grant 2020-A0070800609). N. G. thanks A. de la Lande for providing the deMon2k version with the last cDFT and QM/MM modules and his kind explanations.

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Authors and Affiliations

  1. Indian Institute of Science Education and Research (IISER) Tirupati, Karakambadi Road, Mangalam, Tirupati, Andhra Pradesh, 517507, India

    Ranjitha Ravindranath

  2. Department of Chemistry and Center for Atomic, Molecular and Optical Sciences and Technologies, Indian Institute of Science Education and Research (IISER) Tirupati, Karakambadi Road, Mangalam, Tirupati, Andhra Pradesh, 517507, India

    Padmabati Mondal

  3. Laboratoire de Chimie, CNRS UMR 5182, ENS de Lyon, Université de Lyon, 69342, Lyon, France

    Natacha Gillet

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  1. Ranjitha Ravindranath
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Ravindranath, R., Mondal, P. & Gillet, N. Radical cation transfer in a guanine pair: an insight to the G-quadruplex structure role using constrained DFT/MM. Theor Chem Acc 140, 89 (2021). https://doi.org/10.1007/s00214-021-02787-0

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