Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles
This paper represents generalization of the novel tautomerization mechanism of the G•T/G•U nucleobase pairs – quantum transformation of the standard wobble G•T(w)/G•U(w) base pairs into the Watson–Crick-like (WC) structures: G•T(w)/G•U(w)→G•T*(WC)/G•U*(WC)→G*•T(WC)/G*•U(WC) (here * defines the mutag...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
|
| Series: | Chemical Physics Impact |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022420300062 |
| _version_ | 1818876333353074688 |
|---|---|
| author | Ol’ha O. Brovarets Dmytro M. Hovorun |
| author_facet | Ol’ha O. Brovarets Dmytro M. Hovorun |
| author_sort | Ol’ha O. Brovarets |
| collection | DOAJ |
| description | This paper represents generalization of the novel tautomerization mechanism of the G•T/G•U nucleobase pairs – quantum transformation of the standard wobble G•T(w)/G•U(w) base pairs into the Watson–Crick-like (WC) structures: G•T(w)/G•U(w)→G•T*(WC)/G•U*(WC)→G*•T(WC)/G*•U(WC) (here * defines the mutagenic tautomeric state of the nucleobase) obtained at the MP2/6-311++G(2df,pd) // B3LYP/6-311++G(d,p) level of theory in vacuum (ε=1) and in the continuum with ε=4 under normal conditions. This transition proceeds through the transition state as a tight zwitterionic base pair – G+•T-/G+•U- (protonated guanine (G+) bounded with deprotonated thymine/uracil (T−/U−)). This tautomerization process occurs through the sequential proton transfer within the base pair followed by the shifting of the bases according each other. These data enable to understand the mechanism of the adaptation of the wobble G•T/G•U nucleobase pairs to the Watson–Crick-like geometry of the classical A•T(U)/G•C nucleobase pairs for the successful incorporation into the DNA/RNA duplex, leading to spontaneous point mutations. Based on this data it was reliably explained the origin of the spontaneous and induced by 5BrU molecule point mutations, in particular incorporation errors. It was also detected that the low-polar environment, which is characteristic for the interfaces of the biomolecular interactions, slows down these tautomerization processes due to the increasing of the energetical barriers. Finally, perspectives and ideas according further applications of this model have been provided. We sincerely believe that this investigation will give a significant boost to the development of the field of physical chemistry of nucleic acids, as well as related disciplines such as medicinal chemistry, health research, quantum biology, spectroscopy, crystallography and bioinformatics. This finding also allows to understand in more details the structure, dynamics and functions of DNA and RNA macromolecules by considering their quantum behavior. |
| first_indexed | 2024-12-19T13:40:43Z |
| format | Article |
| id | doaj.art-c35cc7836d77420a980a094f3f421321 |
| institution | Directory Open Access Journal |
| issn | 2667-0224 |
| language | English |
| last_indexed | 2024-12-19T13:40:43Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj.art-c35cc7836d77420a980a094f3f4213212022-12-21T20:19:02ZengElsevierChemical Physics Impact2667-02242020-12-011100006Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological rolesOl’ha O. Brovarets0Dmytro M. Hovorun1Corresponding author.; Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnoho Street, 03680 Kyiv, UkraineDepartment of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnoho Street, 03680 Kyiv, UkraineThis paper represents generalization of the novel tautomerization mechanism of the G•T/G•U nucleobase pairs – quantum transformation of the standard wobble G•T(w)/G•U(w) base pairs into the Watson–Crick-like (WC) structures: G•T(w)/G•U(w)→G•T*(WC)/G•U*(WC)→G*•T(WC)/G*•U(WC) (here * defines the mutagenic tautomeric state of the nucleobase) obtained at the MP2/6-311++G(2df,pd) // B3LYP/6-311++G(d,p) level of theory in vacuum (ε=1) and in the continuum with ε=4 under normal conditions. This transition proceeds through the transition state as a tight zwitterionic base pair – G+•T-/G+•U- (protonated guanine (G+) bounded with deprotonated thymine/uracil (T−/U−)). This tautomerization process occurs through the sequential proton transfer within the base pair followed by the shifting of the bases according each other. These data enable to understand the mechanism of the adaptation of the wobble G•T/G•U nucleobase pairs to the Watson–Crick-like geometry of the classical A•T(U)/G•C nucleobase pairs for the successful incorporation into the DNA/RNA duplex, leading to spontaneous point mutations. Based on this data it was reliably explained the origin of the spontaneous and induced by 5BrU molecule point mutations, in particular incorporation errors. It was also detected that the low-polar environment, which is characteristic for the interfaces of the biomolecular interactions, slows down these tautomerization processes due to the increasing of the energetical barriers. Finally, perspectives and ideas according further applications of this model have been provided. We sincerely believe that this investigation will give a significant boost to the development of the field of physical chemistry of nucleic acids, as well as related disciplines such as medicinal chemistry, health research, quantum biology, spectroscopy, crystallography and bioinformatics. This finding also allows to understand in more details the structure, dynamics and functions of DNA and RNA macromolecules by considering their quantum behavior.http://www.sciencedirect.com/science/article/pii/S2667022420300062DNA/RNAWobble↔Watson–Crick tautomerizationTautomeric hypothesisTautomeric transformationG•T/G•U nucleobase pairs5BrU molecule |
| spellingShingle | Ol’ha O. Brovarets Dmytro M. Hovorun Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles Chemical Physics Impact DNA/RNA Wobble↔Watson–Crick tautomerization Tautomeric hypothesis Tautomeric transformation G•T/G•U nucleobase pairs 5BrU molecule |
| title | Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles |
| title_full | Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles |
| title_fullStr | Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles |
| title_full_unstemmed | Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles |
| title_short | Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles |
| title_sort | quantum dancing of the wobble g•t u 5bru nucleobase pairs and its biological roles |
| topic | DNA/RNA Wobble↔Watson–Crick tautomerization Tautomeric hypothesis Tautomeric transformation G•T/G•U nucleobase pairs 5BrU molecule |
| url | http://www.sciencedirect.com/science/article/pii/S2667022420300062 |
| work_keys_str_mv | AT olhaobrovarets quantumdancingofthewobblegtu5brunucleobasepairsanditsbiologicalroles AT dmytromhovorun quantumdancingofthewobblegtu5brunucleobasepairsanditsbiologicalroles |