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T. A. Zubatiuk et al.
The presence of polar environment around the deoxyribonucleotides significantly affects the relative stability of their conformers. In the case of mTMP and
mCMP molecules the N/anti-conformation is most advantageous in terms of the
relative energy, whereas in the case of mAMP and mGMP the S/syn conformation
is the most preferable. The difference in conformer’s energies changes noticeable
in polar solvent.
An incorporation of nucleotides into A-DNA macromolecules requires the
smallest deformation energy. Nucleotides mAMP and mGMP undergo the greatest
deformations, during their incorporation into Z-DNA. Change of DNTs conformation causes switch between different types of intramolecular H-bonds and results in
different energetic effects for purine and pyrimidine during their incorporation into
DNA structure. Every type of DNA possesses unique set of intramolecular hydrogen bonds in nucleotides.
Protonation of nucleobases in anions of canonical 2′-deoxyribonucleotides demonstrated that this process leads to significant decrease of conformational space of
purine nucleotides. Interestingly, almost all conformers found for non-protonated
molecules correspond to minima of the potential energy surface for protonated
mTMP and mCMP. However, in all nucleotides, only one conformer is populated. It
concerns all tautomers of protonated molecules except of mTMP and mCMP with
the proton attached to the carbonyl group. In these two cases also a minor population of second conformer is observed. Protonation of nucleobase leads to significant
elongation of the N-glycosidic bond. These findings agree well with suggestions
that protonation of nucleobase is a first step in cleavage of the glycosidic bond. The
oxygen atoms of both carbonyl groups of thymine and the N3 atom of the pyrimidine ring of cytosine, guanine, and adenine represent the most preferable sites for
protonation of anions of 2′-deoxyrobonucleotides. The highest proton affinity is
observed for the base in mGMP and the lowest for the thymine moiety in mTMP. It
should be noted that calculated values of the proton affinities in anionic nucleotides
are significantly higher (by 2−3 eV) than for nucleosides and neutral nucleotides.
This emphasizes that the proton affinity of the base in DNA macromolecule may
be tuned by changing the extent of shielding or neutralization of negative charge of
the phosphate group.
Relationship between the conformational dynamics of nucleotides and their tautomeric transitions demonstrated that deprotonization of nucleobase is carried out
due to rotation of nucleobase around the glycosidic bond. This leads to the proton
transfer from the nitrogen atom of nucleobase to the oxygen atom of the phosphate
group. Such deformation of the geometry of the molecule prevent the formation of
a strong C8–H...O hydrogen bond, in order to deactivate the nucleobase`s carbon
atom C8. This carbon is the most preferred for bonding in oxidation reaction, particularly in the process of oxidative damage of DNA chain.
Acknowledgments The authors thank the National Science Foundation for financial support
through NSF/CREST Award (HRD-0833178). This research was supported in part by the Extreme
Science and Engineering Discovery Environment (XSEDE) by National Science Foundation grant
number OCI-1053575 and XSEDE award allocation number DMR110088. Authors thank to the
Mississippi Center for Supercomputer Research (Oxford, MS) for the generous allotment of com-
T. A. Zubatiuk et al.
The presence of polar environment around the deoxyribonucleotides significantly affects the relative stability of their conformers. In the case of mTMP and
mCMP molecules the N/anti-conformation is most advantageous in terms of the
relative energy, whereas in the case of mAMP and mGMP the S/syn conformation
is the most preferable. The difference in conformer’s energies changes noticeable
in polar solvent.
An incorporation of nucleotides into A-DNA macromolecules requires the
smallest deformation energy. Nucleotides mAMP and mGMP undergo the greatest
deformations, during their incorporation into Z-DNA. Change of DNTs conformation causes switch between different types of intramolecular H-bonds and results in
different energetic effects for purine and pyrimidine during their incorporation into
DNA structure. Every type of DNA possesses unique set of intramolecular hydrogen bonds in nucleotides.
Protonation of nucleobases in anions of canonical 2′-deoxyribonucleotides demonstrated that this process leads to significant decrease of conformational space of
purine nucleotides. Interestingly, almost all conformers found for non-protonated
molecules correspond to minima of the potential energy surface for protonated
mTMP and mCMP. However, in all nucleotides, only one conformer is populated. It
concerns all tautomers of protonated molecules except of mTMP and mCMP with
the proton attached to the carbonyl group. In these two cases also a minor population of second conformer is observed. Protonation of nucleobase leads to significant
elongation of the N-glycosidic bond. These findings agree well with suggestions
that protonation of nucleobase is a first step in cleavage of the glycosidic bond. The
oxygen atoms of both carbonyl groups of thymine and the N3 atom of the pyrimidine ring of cytosine, guanine, and adenine represent the most preferable sites for
protonation of anions of 2′-deoxyrobonucleotides. The highest proton affinity is
observed for the base in mGMP and the lowest for the thymine moiety in mTMP. It
should be noted that calculated values of the proton affinities in anionic nucleotides
are significantly higher (by 2−3 eV) than for nucleosides and neutral nucleotides.
This emphasizes that the proton affinity of the base in DNA macromolecule may
be tuned by changing the extent of shielding or neutralization of negative charge of
the phosphate group.
Relationship between the conformational dynamics of nucleotides and their tautomeric transitions demonstrated that deprotonization of nucleobase is carried out
due to rotation of nucleobase around the glycosidic bond. This leads to the proton
transfer from the nitrogen atom of nucleobase to the oxygen atom of the phosphate
group. Such deformation of the geometry of the molecule prevent the formation of
a strong C8–H...O hydrogen bond, in order to deactivate the nucleobase`s carbon
atom C8. This carbon is the most preferred for bonding in oxidation reaction, particularly in the process of oxidative damage of DNA chain.
Acknowledgments The authors thank the National Science Foundation for financial support
through NSF/CREST Award (HRD-0833178). This research was supported in part by the Extreme
Science and Engineering Discovery Environment (XSEDE) by National Science Foundation grant
number OCI-1053575 and XSEDE award allocation number DMR110088. Authors thank to the
Mississippi Center for Supercomputer Research (Oxford, MS) for the generous allotment of com-