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V. Poltev et al.
of directionality and presence of preferable regions in the sugar-phosphate torsions
combined with the difference of purines from pyrimidines in ring shape. It appears
that along with other three-dimensional DNA structures, experimentally studied fragments of DNA contain variety of cdDMPs with Watson-Crick nucleoside pairs but
with one or both dDMPs belonging to conformational families different from A and
B. Comprehensive analysis of conformational characteristics of such cdDMP belonging to select families by using various computational methods, and the comparison of
subunit contributions to their three-dimensional structure formation suggested that
the regularities for the most of such cdDMPs differ from those of ‘canonical’ WCD.
The geometry of the optimized conformations of those cdDMPs depends on the used
computational method, and sometimes departs from the double helix structure. Comparison of the results including those from optimization of cdDMPs, dDMPs, SPB,
and base-base pairwise interactions against the mutual position of DNA subunits
in crystals shows that none of the computational methods is able to quantitatively
describe all experimental structures of DNA, and to correctly reproduce the interaction between its subunits. Analysis of these data produces valuable information about
the strengths and limitations of the employed computational methods, and suggests
the pathway for their improvement. The work concludes that the complex interplay
that exists between the DNA subunits requires additional investigations by using
multiple computational methods each targeting particular aspects of the system.
Keywords Computer simulation · MM · QM · DFT · 3D-structure · Regularity ·
Multiplicity · Variability · Flexibility · Canonical · DNA · Nucleotide · Base pair
interaction · Deoxyribose · Sugar-phosphate backbone · Hydrophilic ·
Hydrophobic · WCD · SPB · dApdG · dTpdC · cdDMP · dDMP
1 Introduction. Complexity and Simplicity of the Most
Important Molecule of Life
DNA is the most important macromolecule of life. The sequence of monomer units
composing the long polynucleotide chain of DNA contains all the information necessary for functioning of live organisms. Despite the enormous biological role of
DNA, its chemical composition is limited to a linear arrangement of four nucleotides
in the chain consisting of many thousands of monomers. Such seemingly simple
construction encodes the infinite diversity of life. Figure 1 presents a fragment of
DNA chain consisting of four possible nucleotides.
The fragment shown in Fig. 1 is usually designated as dApdTpdGpdC. Each
nucleotide in it contains three subunits, namely, a nitrogenous base, deoxyribose,
and phosphate group. Among those units, DNA base is the only variable part in
the nucleotide, while deoxyribose and phosphate form chemically homogeneous
sugar-phosphate backbone, SPB. We will designate bases and nucleosides, which
compose bases connected to sugar moiety via N-glycoside bond, by a single letter.
Two of the bases are purines: adenine, (A), and guanine, (G); and other two bases are
V. Poltev et al.
of directionality and presence of preferable regions in the sugar-phosphate torsions
combined with the difference of purines from pyrimidines in ring shape. It appears
that along with other three-dimensional DNA structures, experimentally studied fragments of DNA contain variety of cdDMPs with Watson-Crick nucleoside pairs but
with one or both dDMPs belonging to conformational families different from A and
B. Comprehensive analysis of conformational characteristics of such cdDMP belonging to select families by using various computational methods, and the comparison of
subunit contributions to their three-dimensional structure formation suggested that
the regularities for the most of such cdDMPs differ from those of ‘canonical’ WCD.
The geometry of the optimized conformations of those cdDMPs depends on the used
computational method, and sometimes departs from the double helix structure. Comparison of the results including those from optimization of cdDMPs, dDMPs, SPB,
and base-base pairwise interactions against the mutual position of DNA subunits
in crystals shows that none of the computational methods is able to quantitatively
describe all experimental structures of DNA, and to correctly reproduce the interaction between its subunits. Analysis of these data produces valuable information about
the strengths and limitations of the employed computational methods, and suggests
the pathway for their improvement. The work concludes that the complex interplay
that exists between the DNA subunits requires additional investigations by using
multiple computational methods each targeting particular aspects of the system.
Keywords Computer simulation · MM · QM · DFT · 3D-structure · Regularity ·
Multiplicity · Variability · Flexibility · Canonical · DNA · Nucleotide · Base pair
interaction · Deoxyribose · Sugar-phosphate backbone · Hydrophilic ·
Hydrophobic · WCD · SPB · dApdG · dTpdC · cdDMP · dDMP
1 Introduction. Complexity and Simplicity of the Most
Important Molecule of Life
DNA is the most important macromolecule of life. The sequence of monomer units
composing the long polynucleotide chain of DNA contains all the information necessary for functioning of live organisms. Despite the enormous biological role of
DNA, its chemical composition is limited to a linear arrangement of four nucleotides
in the chain consisting of many thousands of monomers. Such seemingly simple
construction encodes the infinite diversity of life. Figure 1 presents a fragment of
DNA chain consisting of four possible nucleotides.
The fragment shown in Fig. 1 is usually designated as dApdTpdGpdC. Each
nucleotide in it contains three subunits, namely, a nitrogenous base, deoxyribose,
and phosphate group. Among those units, DNA base is the only variable part in
the nucleotide, while deoxyribose and phosphate form chemically homogeneous
sugar-phosphate backbone, SPB. We will designate bases and nucleosides, which
compose bases connected to sugar moiety via N-glycoside bond, by a single letter.
Two of the bases are purines: adenine, (A), and guanine, (G); and other two bases are