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Article

Stability and Cations Coordination of DNA and RNA 14-Mer G-Quadruplexes: A Multiscale Computational Approach

Supporting Info

Bruno Pagano^†, Carlo A. Mattia^†, Luigi Cavallo^‡, Seiichi Uesugi^§, Concetta Giancola and Franca Fraternali*

Dipartimento di Scienze Farmaceutiche, Universit

di Salerno, via Ponte Don Melillo, Fisciano (SA), I-84084, Italy, Dipartimento di Chimica, Universit

di Salerno, via Ponte Don Melillo, Fisciano (SA), I-84084, Italy, Department of Environment and Natural Sciences, Yokohama National University, 79-7 Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan, Dipartimento di Chimica, Universit

di Napoli Federico II, via Cintia, Napoli, I-80126, Italy, and The Randall Division of Cell and Molecular Biophysics, New Hunt’s House, SE1 1UL, London, U.K.

J. Phys. Chem. B, 2008, 112 (38), pp 12115–12123

DOI: 10.1021/jp804036j

Publication Date (Web): September 3, 2008

†

Dipartimento di Scienze Farmaceutiche, Universit di Salerno.

‡

Dipartimento di Chimica, Universit di Salerno.

Department of Environment and Natural Sciences.

Dipartimento di Chimica, Universit di Napoli Federico II.

* Corresponding author. E-mail franca.fraternali@kcl.ac.uk.

The Randall Division of Cell and Molecular Biophysics.

Abstract

Molecular dynamics simulations have been used to study the differences between two DNA and RNA 14-mer quadruplexes of analogous sequences. Their structures present a completely different fold: DNA forms a bimolecular quadruplex containing antiparallel strands and diagonal loops; RNA forms an intrastrand parallel quadruplex containing a G-tetrad and an hexad, which dimerizes by hexad stacking. We used a multiscale computational approach combining classical Molecular dynamics simulations and density functional theory calculations to elucidate the difference in stability of the 2-folds and their ability in coordinating cations. The presence of 2′-OH groups in the RNA promotes the formation of a large number of intramolecular hydrogen bonds that account for the difference in fold and stability of the two 14-mers. We observe that the adenines in the RNA quadruplex play a key role in conserving the geometry of the hexad. We predict the cation coordination mode of the two quadruplexes, not yet observed experimentally, and we offer a rationale for the corresponding binding energies involved.

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