138
T. A. Zubatiuk et al.
It is based on the analysis of consequences of nucleobases protonation along with
the details of intramolecular interactions in 2’-deoxyribonucleotide anions. The
results of our molecular simulations cast light on relationship between the conformational dynamics of a molecule and the tautomeric transitions in the components
of nucleotides.
5.1 Introduction
The canonical 2′-deoxyribonucleotides (DNTs) represent the monomeric unit of
DNA macromolecules [1–3]. Substituted or modified nucleotides are widely used
as antibiotics, hormones, coenzymes, etc. [1–5]. In addition, nucleotides have other,
independent functions of being cofactors, allosteric effectors, they are incorporated
into coenzymes and directly involved into metabolic and accumulation processes,
as well as into energy transfer. Nucleosides and nucleotides interact with proteins in
all stages of their metabolism. Interestingly, the derivatives of adenosine in living
cells perform a variety of biological functions, e.g. they are the inhibitors of protein
synthesis. In the form of di- and triphosphate, adenosine is the energy source for
a set of enzymatic reactions and muscle contractions. Therefore, knowledge of the
structure and nature of intermolecular interactions in nucleotides is essential for
understanding of the molecular mechanisms that take place in living cells.
The structures of monomeric DNTs and their derivatives were extensively studied by experimental methods—mainly by X-ray diffraction [6–8] and NMR spectroscopy [9]. Information concerning the structure of DNTs as building blocks of
DNA was derived from experimental data for various oligonucleotides. As a result
of such studies it is generally accepted that nucleotides are not rigid molecules
[10–12]. The nonrigidity of nucleotides is described by the rotation of the nucleobase and furanose moiety relative to each other around the corresponding σ-bonds,
and the phenomenon of the pseudorotation of the furanose ring. It was also demonstrated that DNTs adopt two preferable conformations which have close orientation
of the nucleobase and phosphate with respect to sugar moiety, but have different
conformations of the furanose ring. This finding was supported by ab initio quantum chemical investigations of the molecular structure of DNTs [12–18].
Typically, the experimental studies of DNTs were carried out in the condensed
states where their conformations are significantly affected by intermolecular interactions (hydrogen bonds, interactions with counter ions). This makes uncertain
what exactly have been studied and taken into account: intramolecular properties of
DNTs or the influence of the environment on molecular structure of DNTs. Therefore, experimental data may not reflect the intrinsic conformational properties of
DNTs. Such information may be obtained using gas phase experiments. However,
this information is not available for 2′-deoxyribonucleotides. Therefore, in this case
a missing data could be obtained from investigation of the intrinsic conformational
characteristics of DNTs using computational methods.
Ab initio quantum chemical methods allow not only to calculate the equilibrium geometry, but also to examine the nature of the electron density distribution in
T. A. Zubatiuk et al.
It is based on the analysis of consequences of nucleobases protonation along with
the details of intramolecular interactions in 2’-deoxyribonucleotide anions. The
results of our molecular simulations cast light on relationship between the conformational dynamics of a molecule and the tautomeric transitions in the components
of nucleotides.
5.1 Introduction
The canonical 2′-deoxyribonucleotides (DNTs) represent the monomeric unit of
DNA macromolecules [1–3]. Substituted or modified nucleotides are widely used
as antibiotics, hormones, coenzymes, etc. [1–5]. In addition, nucleotides have other,
independent functions of being cofactors, allosteric effectors, they are incorporated
into coenzymes and directly involved into metabolic and accumulation processes,
as well as into energy transfer. Nucleosides and nucleotides interact with proteins in
all stages of their metabolism. Interestingly, the derivatives of adenosine in living
cells perform a variety of biological functions, e.g. they are the inhibitors of protein
synthesis. In the form of di- and triphosphate, adenosine is the energy source for
a set of enzymatic reactions and muscle contractions. Therefore, knowledge of the
structure and nature of intermolecular interactions in nucleotides is essential for
understanding of the molecular mechanisms that take place in living cells.
The structures of monomeric DNTs and their derivatives were extensively studied by experimental methods—mainly by X-ray diffraction [6–8] and NMR spectroscopy [9]. Information concerning the structure of DNTs as building blocks of
DNA was derived from experimental data for various oligonucleotides. As a result
of such studies it is generally accepted that nucleotides are not rigid molecules
[10–12]. The nonrigidity of nucleotides is described by the rotation of the nucleobase and furanose moiety relative to each other around the corresponding σ-bonds,
and the phenomenon of the pseudorotation of the furanose ring. It was also demonstrated that DNTs adopt two preferable conformations which have close orientation
of the nucleobase and phosphate with respect to sugar moiety, but have different
conformations of the furanose ring. This finding was supported by ab initio quantum chemical investigations of the molecular structure of DNTs [12–18].
Typically, the experimental studies of DNTs were carried out in the condensed
states where their conformations are significantly affected by intermolecular interactions (hydrogen bonds, interactions with counter ions). This makes uncertain
what exactly have been studied and taken into account: intramolecular properties of
DNTs or the influence of the environment on molecular structure of DNTs. Therefore, experimental data may not reflect the intrinsic conformational properties of
DNTs. Such information may be obtained using gas phase experiments. However,
this information is not available for 2′-deoxyribonucleotides. Therefore, in this case
a missing data could be obtained from investigation of the intrinsic conformational
characteristics of DNTs using computational methods.
Ab initio quantum chemical methods allow not only to calculate the equilibrium geometry, but also to examine the nature of the electron density distribution in