Journal of Biomolecular Structure & Dynamics, 2015
This paper is a logical continuation of the theoretical survey of the CH...O/N specific contacts ... more This paper is a logical continuation of the theoretical survey of the CH...O/N specific contacts in the nucleobase pairs using a wide arsenal of the modern methods, which was initiated in our previous study [J. Biomol. Struct. & Dynam., 2014, 32, 993–1022]. It was established that 34 CH...O and 7 CH...N interactions, that were detected by quantum-chemical calculations in the 39 biologically important pairs involving modified nucleobases, completely satisfy all geometrical, vibrational, electron-topological, in particular Bader’s and two-molecule Koch and Popelier’s, Grunenberg’s compliance constants theory and natural bond orbital criteria indicating that they can be identified as true H-bonds. The geometrical criteria of the H-bond formation are fulfilled for all considered CH...O/N H-bonds without any exception. It was shown that the classical rule of the stretching vibration shifts does not work in the 95% cases of the CH...O/N H-bonds. Furthermore, significant increase in the frequency of the out-of-plane deformation modes under the formation of CH...O/N H-bonds and corresponding changes of their intensities can be also considered as reliable indicators of the H-bonding. The studies reported here advance our understanding of the biological role of the weak CH...O/N H-bonds, that dictates the requirements for the structural and dynamical similarity of the canonical and mismatched pairs with Watson–Crick (WC) geometry, which facilitates their enzymatic incorporation into the DNA double helix during DNA replication. Thus, these H-bonds in the base pairs with WC geometry may be also considered as “the last drop” at the transmission of the electronic signal that launches the chemical incorporation of the incoming nucleoside triphosphate into DNA.
Chemistry (Weinheim an der Bergstrasse, Germany), Jan 8, 2017
Anion-π interactions have been shown to stabilize flavoproteins and to regulate the redox potenti... more Anion-π interactions have been shown to stabilize flavoproteins and to regulate the redox potential of the flavin cofactor. They are commonly attributed to electrostatic forces. Herein we show that anion-flavin interactions can have a substantial charge-transfer component. Our conclusion emanates from a multi-approach theoretical analysis and is backed by previously reported observations of absorption bands, originating from charge transfer between oxidized flavin and proximate cysteine thiolate groups. This partial covalency of anion-flavin contacts renders classical simulations of flavoproteins questionable.
The influence of various sugar-residue modifications on intrinsic energetic, conformational, and ... more The influence of various sugar-residue modifications on intrinsic energetic, conformational, and mechanical properties of 2´-deoxyribonucleotide-5´-monophosphates (dNs) was comprehensively investigated using modern quantum chemical approaches. In total, fourteen sugar modifications, including double bonds and heteroatoms (S, N) inside the sugar ring, as well as fluorination in various positions, were analyzed. Among hundreds of possible conformational states of dNs, only two - AI and BI, corresponding to the most biologically significant forms of a double-helical DNA, were considered for each dN. It was established that the most of the studied modifications tend to strongly stabilize either AI or BI conformation of dNs both in the gas phase and in aqueous solution (modeled by implicit solvent models). Therefore, some of these modifications can be used as a tool for reducing structural polymorphism of nucleic acids in solution as well as for designing oligonucleotides with specific structural features. The evaluation of relaxed force constants (RFC) for glycosidic bonds suggests that the majority of the studied modifications of the sugar residue yield increased strengths of glycosidic bonds in dNs, and can therefore be used for designing modified nucleic acids with an increased resistance to abasic lesions. The most significant reinforcement of the glycosidic bond occurs in dNs containing the CF2 group instead of the O4' oxygen and the fluorine atom at the 2'-alpha-position. The calculation of the RFC and vibrational root-mean-square (VRMS) deviations for conformational degrees of freedom revealed a strong dependence between mechanical properties of dNs and their energetic characteristics. In particular, electronic energies of AI and BI conformers of dNs calculated in vacuo are closely connected with the values of relaxed force constants (RFC) for the delta angle: the higher RFC(delta) values correspond to more energetically favorable conformers.
Journal of Biomolecular Structure & Dynamics, 2015
This paper is a logical continuation of the theoretical survey of the CH...O/N specific contacts ... more This paper is a logical continuation of the theoretical survey of the CH...O/N specific contacts in the nucleobase pairs using a wide arsenal of the modern methods, which was initiated in our previous study [J. Biomol. Struct. & Dynam., 2014, 32, 993–1022]. It was established that 34 CH...O and 7 CH...N interactions, that were detected by quantum-chemical calculations in the 39 biologically important pairs involving modified nucleobases, completely satisfy all geometrical, vibrational, electron-topological, in particular Bader’s and two-molecule Koch and Popelier’s, Grunenberg’s compliance constants theory and natural bond orbital criteria indicating that they can be identified as true H-bonds. The geometrical criteria of the H-bond formation are fulfilled for all considered CH...O/N H-bonds without any exception. It was shown that the classical rule of the stretching vibration shifts does not work in the 95% cases of the CH...O/N H-bonds. Furthermore, significant increase in the frequency of the out-of-plane deformation modes under the formation of CH...O/N H-bonds and corresponding changes of their intensities can be also considered as reliable indicators of the H-bonding. The studies reported here advance our understanding of the biological role of the weak CH...O/N H-bonds, that dictates the requirements for the structural and dynamical similarity of the canonical and mismatched pairs with Watson–Crick (WC) geometry, which facilitates their enzymatic incorporation into the DNA double helix during DNA replication. Thus, these H-bonds in the base pairs with WC geometry may be also considered as “the last drop” at the transmission of the electronic signal that launches the chemical incorporation of the incoming nucleoside triphosphate into DNA.
Chemistry (Weinheim an der Bergstrasse, Germany), Jan 8, 2017
Anion-π interactions have been shown to stabilize flavoproteins and to regulate the redox potenti... more Anion-π interactions have been shown to stabilize flavoproteins and to regulate the redox potential of the flavin cofactor. They are commonly attributed to electrostatic forces. Herein we show that anion-flavin interactions can have a substantial charge-transfer component. Our conclusion emanates from a multi-approach theoretical analysis and is backed by previously reported observations of absorption bands, originating from charge transfer between oxidized flavin and proximate cysteine thiolate groups. This partial covalency of anion-flavin contacts renders classical simulations of flavoproteins questionable.
The influence of various sugar-residue modifications on intrinsic energetic, conformational, and ... more The influence of various sugar-residue modifications on intrinsic energetic, conformational, and mechanical properties of 2´-deoxyribonucleotide-5´-monophosphates (dNs) was comprehensively investigated using modern quantum chemical approaches. In total, fourteen sugar modifications, including double bonds and heteroatoms (S, N) inside the sugar ring, as well as fluorination in various positions, were analyzed. Among hundreds of possible conformational states of dNs, only two - AI and BI, corresponding to the most biologically significant forms of a double-helical DNA, were considered for each dN. It was established that the most of the studied modifications tend to strongly stabilize either AI or BI conformation of dNs both in the gas phase and in aqueous solution (modeled by implicit solvent models). Therefore, some of these modifications can be used as a tool for reducing structural polymorphism of nucleic acids in solution as well as for designing oligonucleotides with specific structural features. The evaluation of relaxed force constants (RFC) for glycosidic bonds suggests that the majority of the studied modifications of the sugar residue yield increased strengths of glycosidic bonds in dNs, and can therefore be used for designing modified nucleic acids with an increased resistance to abasic lesions. The most significant reinforcement of the glycosidic bond occurs in dNs containing the CF2 group instead of the O4' oxygen and the fluorine atom at the 2'-alpha-position. The calculation of the RFC and vibrational root-mean-square (VRMS) deviations for conformational degrees of freedom revealed a strong dependence between mechanical properties of dNs and their energetic characteristics. In particular, electronic energies of AI and BI conformers of dNs calculated in vacuo are closely connected with the values of relaxed force constants (RFC) for the delta angle: the higher RFC(delta) values correspond to more energetically favorable conformers.
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Papers by Yevgen Yurenko