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Chapter 6
Quantum Chemical Approaches in Modeling
the Structure of DNA Quadruplexes
and Their Interaction with Metal Ions
and Small Molecules
Mykola Ilchenko and Igor Dubey
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_6
I. Dubey () · M. Ilchenko
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine,
150 Zabolotnogo str., 03680 Kyiv, Ukraine
e-mail: dubey@imbg.org.ua
Abstract Certain guanine-rich DNA and RNA sequences can fold into unique biologically significant high-order structures called G-quadruplexes (G4) formed by
stacked arrays of guanine quartets connected by non-canonical hydrogen bonds.
Novel anticancer strategy is based on the use of organic molecules that specifically target quadruplex structures present in telomeres and some other regions of
the genome. We provide a brief overview of the structural features of quadruplex
nucleic acids and main mechanisms of G4-ligand interaction. Current methods for
the molecular modeling of quadruplex DNA structures and their ligand binding
are discussed in the review. We mainly focus on quantum chemical computational
approaches to model the interaction of G4 DNA and its structural elements with
metal cations and small molecules, including hybrid QM/MM approaches.
6.1 Introduction
The molecular basis of the formation of biologically functional structures of biomacromolecules (proteins, nucleic acids, etc.) and their specific interactions with
low-molecular ligands remains one of the most exciting problems of biomedical
science and a foundation of modern drug design.
Quite recently emerged the antitumor strategy based on the use of small molecules that specifically target telomeres and telomerase [1–4]. Telomeres are guanine-rich DNA sequences localized at the ends of the chromosomes. They protect
chromosomal DNA from degradation, prevent end-to-end fusion and other forms
of aberrant recombination, and allow it to be completely replicated without loss of
genetic material. The length of the telomeres correlates with the ability of a cell to
Chapter 6
Quantum Chemical Approaches in Modeling
the Structure of DNA Quadruplexes
and Their Interaction with Metal Ions
and Small Molecules
Mykola Ilchenko and Igor Dubey
© Springer Science+Business Media Dordrecht 2014
L. Gorb et al. (eds.), Application of Computational Techniques in Pharmacy and Medicine,
Challenges and Advances in Computational Chemistry and Physics 17,
DOI 10.1007/978-94-017-9257-8_6
I. Dubey () · M. Ilchenko
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine,
150 Zabolotnogo str., 03680 Kyiv, Ukraine
e-mail: dubey@imbg.org.ua
Abstract Certain guanine-rich DNA and RNA sequences can fold into unique biologically significant high-order structures called G-quadruplexes (G4) formed by
stacked arrays of guanine quartets connected by non-canonical hydrogen bonds.
Novel anticancer strategy is based on the use of organic molecules that specifically target quadruplex structures present in telomeres and some other regions of
the genome. We provide a brief overview of the structural features of quadruplex
nucleic acids and main mechanisms of G4-ligand interaction. Current methods for
the molecular modeling of quadruplex DNA structures and their ligand binding
are discussed in the review. We mainly focus on quantum chemical computational
approaches to model the interaction of G4 DNA and its structural elements with
metal cations and small molecules, including hybrid QM/MM approaches.
6.1 Introduction
The molecular basis of the formation of biologically functional structures of biomacromolecules (proteins, nucleic acids, etc.) and their specific interactions with
low-molecular ligands remains one of the most exciting problems of biomedical
science and a foundation of modern drug design.
Quite recently emerged the antitumor strategy based on the use of small molecules that specifically target telomeres and telomerase [1–4]. Telomeres are guanine-rich DNA sequences localized at the ends of the chromosomes. They protect
chromosomal DNA from degradation, prevent end-to-end fusion and other forms
of aberrant recombination, and allow it to be completely replicated without loss of
genetic material. The length of the telomeres correlates with the ability of a cell to