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Molecular dynamics studies of the 3D structure and planar ligand binding of a quadruplex dimer

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Abstract

G-rich sequences can fold into a four-stranded structure called a G-quadruplex, and sequences with short loops are able to aggregate to form stable quadruplex multimers. Few studies have characterized the properties of this variety of quadruplex multimers. Using molecular modeling and molecular dynamics simulations, the present study investigated a dimeric G-quadruplex structure formed from a simple sequence of d(GGGTGGGTGGGTGGGT) (G1), and its interactions with a planar ligand of a perylene derivative (Tel03). A series of analytical methods, including free energy calculations and principal components analysis (PCA), was used. The results show that a dimer structure with stacked parallel monomer structures is maintained well during the entire simulation. Tel03 can bind to the dimer efficiently through end stacking, and the binding mode of the ligand stacked with the 3′-terminal thymine base is most favorable. PCA showed that the dominant motions in the free dimer occur on the loop regions, and the presence of the ligand reduces the flexibility of the loops. Our investigation will assist in understanding the geometric structure of stacked G-quadruplex multimers and may be helpful as a platform for rational drug design.

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Acknowledgments

This work was supported by the National Science Foundation of China (20973049, 20673044), PCSIRT (IRT0625). We would like to thank professor David A. Case et al. for giving us the Amber 10.0 software as freeware.

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Authors and Affiliations

  1. Institute of Theoretical Chemistry, State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun, 130023, People’s Republic of China

    Ming-Hui Li, Quan Luo, Xiang-Gui Xue & Ze-Sheng Li

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  1. Ming-Hui Li
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  2. Quan Luo
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  3. Xiang-Gui Xue
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Correspondence to Ze-Sheng Li.

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Li, MH., Luo, Q., Xue, XG. et al. Molecular dynamics studies of the 3D structure and planar ligand binding of a quadruplex dimer. J Mol Model 17, 515–526 (2011). https://doi.org/10.1007/s00894-010-0746-0

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  • DOI: https://doi.org/10.1007/s00894-010-0746-0

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