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V. Poltev et al.
bases A and T form two H-bonds, while G and C form three H-bonds. Two complementary antiparallel polynucleotide chains of WCD assemble in right-handed double
helix.
The molecular structure of DNA accommodates various intermolecular and
intramolecular interactions that determine the wealth of its three-dimensional structure, and lead to the formation of complexes with other important biomolecules,
including proteins. Polynucleotide chain and each of its nucleotide units contain
nearly planar and rigid nitrogenous bases shown in the right-hand side of Fig. 1, as
well as flexible SPB shown in the left-hand side of Fig. 1. The nucleotide structure
includes both hydrophilic and hydrophobic atom groups. The hydrophilic N-H and
amino groups of the bases are H-bond donors; whereas oxygen atoms of all three
nucleotide subunits are acceptors. The CH, CH 2 , and CH 3 groups play the role of
hydrophobic units. The phosphate is an electrophilic group that carries a negative
charge at biologically relevant pH conditions.
Since the discovery of DNA double helix by Watson and Crick in 1953 [1] it
became clear that its molecular and three-dimensional organization is surprizingly
fit to the biological functions attributed to the main molecule of life. The 3D structure of DNA supports storage, protection, replication, expression and evolutionary
adjustment of genetic material among other important biological functions. Some
of those features have been noticed right in the beginning and were studied during the first years after Watson and Crick’s discovery. Conformational transitions
between the double-stranded and single-stranded states, the dependence of helix
stability on nucleotide content (due to different number of H-bonds in the two complementary pairs), the possibility of both specific (via H-bonding with the base pairs)
and nonspecific (via negatively charged phosphate groups) interactions with other
biologically important molecules including proteins, are examples of such features.
Other important aspects of the WCD, such as several levels of organization of its
three-dimensional structure, the dependence of its structure on nucleotide sequence,
the regularities of this dependence, the existence of variety of conformation families
with specific regions of the torsion angles of SPB for each family, were understood
a few decades later. In spite of the extensive and thorough investigations of DNA
structure including the mechanism in which its fragments interact one with another,
not everything is sufficiently clear about the contribution of DNA subunits to its
three-dimensional organization and the role that individual atoms and atomic groups
play in the DNA structure and function.
For the last few decades our group has been working on deciphering general
regularities of DNA three-dimensional structure organization via the application of
quantum mechanics (QM) and molecular mechanics (MM) methods to the relatively
simple fragments of DNA. By using density functional theory (DFT) computations,
we demonstrated that the main conformational characteristics of B- and A- WatsonCrick right-handed duplexes preexist in the local energy minima of deoxynucleoside
monophospates (dDMPs), which represent the elemental fragments of DNA single
chain [2–8]. The discovered characteristics of dDMPs depend on nucleoside sequence
and reproduce the similar dependence noticed in the crystals of WCD fragments.
Specifically, base superposition patterns of Pur–Pyr and Pur–Pur sequences differ
V. Poltev et al.
bases A and T form two H-bonds, while G and C form three H-bonds. Two complementary antiparallel polynucleotide chains of WCD assemble in right-handed double
helix.
The molecular structure of DNA accommodates various intermolecular and
intramolecular interactions that determine the wealth of its three-dimensional structure, and lead to the formation of complexes with other important biomolecules,
including proteins. Polynucleotide chain and each of its nucleotide units contain
nearly planar and rigid nitrogenous bases shown in the right-hand side of Fig. 1, as
well as flexible SPB shown in the left-hand side of Fig. 1. The nucleotide structure
includes both hydrophilic and hydrophobic atom groups. The hydrophilic N-H and
amino groups of the bases are H-bond donors; whereas oxygen atoms of all three
nucleotide subunits are acceptors. The CH, CH 2 , and CH 3 groups play the role of
hydrophobic units. The phosphate is an electrophilic group that carries a negative
charge at biologically relevant pH conditions.
Since the discovery of DNA double helix by Watson and Crick in 1953 [1] it
became clear that its molecular and three-dimensional organization is surprizingly
fit to the biological functions attributed to the main molecule of life. The 3D structure of DNA supports storage, protection, replication, expression and evolutionary
adjustment of genetic material among other important biological functions. Some
of those features have been noticed right in the beginning and were studied during the first years after Watson and Crick’s discovery. Conformational transitions
between the double-stranded and single-stranded states, the dependence of helix
stability on nucleotide content (due to different number of H-bonds in the two complementary pairs), the possibility of both specific (via H-bonding with the base pairs)
and nonspecific (via negatively charged phosphate groups) interactions with other
biologically important molecules including proteins, are examples of such features.
Other important aspects of the WCD, such as several levels of organization of its
three-dimensional structure, the dependence of its structure on nucleotide sequence,
the regularities of this dependence, the existence of variety of conformation families
with specific regions of the torsion angles of SPB for each family, were understood
a few decades later. In spite of the extensive and thorough investigations of DNA
structure including the mechanism in which its fragments interact one with another,
not everything is sufficiently clear about the contribution of DNA subunits to its
three-dimensional organization and the role that individual atoms and atomic groups
play in the DNA structure and function.
For the last few decades our group has been working on deciphering general
regularities of DNA three-dimensional structure organization via the application of
quantum mechanics (QM) and molecular mechanics (MM) methods to the relatively
simple fragments of DNA. By using density functional theory (DFT) computations,
we demonstrated that the main conformational characteristics of B- and A- WatsonCrick right-handed duplexes preexist in the local energy minima of deoxynucleoside
monophospates (dDMPs), which represent the elemental fragments of DNA single
chain [2–8]. The discovered characteristics of dDMPs depend on nucleoside sequence
and reproduce the similar dependence noticed in the crystals of WCD fragments.
Specifically, base superposition patterns of Pur–Pyr and Pur–Pur sequences differ