Tag Archives: quantum-chemical calculations

Conformational capacity of 2′,3′-didehydro-2′,3′-dideoxyadenosine as a key to understanding its biological activity: results of quantum chemical modelling

 

A. G. Ponomareva1, Ye. P. Yurenko1, R. O. Zhurakivsky1, D. M. Hovorun1,2

1Institute of Molecular Biology and Genetics, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: yevgen.yurenko@gmail.com;
2Institute of High Technologies, Taras Shevchenko Kyiv
National University, Ukraine

Comprehensive conformational analysis of the biologically active nucleoside 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A) has been performed at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and polar characteristics of twenty one d4A conformers as well as their conformational equilibrium were investigated. The electron density topological analysis allowed us to establish that the d4A molecule is stabilized by eight types of intramolecular interactions: O5′H…N3, O5′H…C8, C8H…O5′, C2′H…N3, C5′H1…N3, C5′H2…N3 та C8H…H1/2C5′. The obtained results of conformational analysis lead us to think that d4A may be a terminator of the DNA chain sythesis in the 5′-3′ direction. Thus it can be inferred that d4A competes with canonical 2′-deoxyadenosine in binding an active site of the corresponding enzyme.

Complete conformational family of 2′,3′-didehydro-2′,3′-dideoxyguanosine: quantum chemical and electron density topological study

A. G. Ponomareva1, Ye. P. Yurenko1,2,3, R. O. Zhurakivsky1,2, D. M. Hovorun1,2,3

1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
e-mail: yevgen.yurenko@gmail.com;
2Research and educational center “State key laboratory of molecular and cell biology”, Kyiv, Ukraine;
3Taras Shevchenko Kyiv National University, Institute of High Technologies, Ukraine;
e-mail: dhovorun@imbg.org.ua

Comprehensive conformational analysis of the biologically active nucleoside 2′,3′-didehydro-2′,3′-dideoxyaguanosine (d4G) has been performed at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and polar characteristics of twenty d4G conformers as well as their conformational equilibrium were investigated. The electron density topological analysis allowed us to establish that the d4G molecule is stabilized by nine types of intramolecular interactions: O5′H…N3, O5′H…C8, C8H…O5′, C2′H…N3, C5′H1…N3, C5′H2…N3, C8H…H1C5′, С8Н…Н2′С5′ and N2H1…O5′. The obtained results of conformational analysis permit us to think that d4G may be a terminator of the DNA chain synthesis in the 5′-3′ direction. Thus it can be inferred that d4G competes with canonical 2′-deoxyaguanosine in binding an active site of the corresponding enzyme.

Structural and energetic properties of the four configurations of the А•Т and G•C DNA base pairs

O. O. Brovarets’

Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
Research and Educational Center “State Key Laboratory of Molecular and Cell Biology”, Kyiv, Ukraine;
Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: brovarets@list.ru

Using the methods of non-empirical quantum chemistry at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory it was established for the first time, that Hoogsteen, reverse Hoogsteen, Watson-Crick and reverse Watson-Crick configurations of the A·T and G·C DNA base pairs are isoelectronic and isomorphic structures with similar dynamic properties. Based on these results, non-ionisation mechanism of the Hoogsteen “breathing” of the G·C DNA base pair, namely transformation of the tautomerised (Löwdin’s) G*·C* base pair with Watson-Crick geometry into the Hoogsteen electroneutral G*·C* H base pair stabilized by the three O6H…N4, N3H…N7 and C8H…O2 H-bonds, was postulated. It is suggested that such scenario activates only in those cases, when DNA is not located in aqueous solution, but works together with proteins and cytosine protonation at the N3 atom is precluded.

Under what conditions does G•C watson-crick DNA base pair acquire all four configurations characteristic for A•T watson-crick DNA base pair?

O. O. Brovarets’

Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv;
Research and Educational Center “State Key Laboratory of Molecular and Cell Biology”, Kyiv, Ukraine;
Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: brovarets@list.ru

At the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory it was established for the first time, that the Löwdin’s G*·C* DNA base pair formed by the mutagenic tautomers can acquire, as the A·T Watson-Crick DNA base pair, four biologically important configurations, namely: Watson-Crick, reverse Watson-Crick, Hoogsteen and reverse Hoogsteen. This fact demonstrates rather unexpected role of the tautomerisation of the one of the Watson-Crick DNA base pairs, in particular, via double proton transfer: exactly the G·C→G*·C* tautomerisation allows to overcome steric hindrances for the implementation of the above mentioned configurations. Geometric, electron-topological and energetic properties of the H-bonds that stabilise the studied pairs, as well as the energetic characteristics of the latters are presented.