Department of Molecular and Quantum Biophysics

Head

Dmytro M. Hovorun

Professor, Dr. Sci. (Mol. Biol.),
Corresponding Member of NASU,
Deputy director for scientific research
Phone: (380-44) 526-11-09; 526-20-14;
fax: (380-44) 526-07-59.
E-mail: dhovorun@imbg.org.ua

Education and Degrees:

1967–1972 Graduate Student, Faculty of Radiophysics, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine M.Sc. (nonlinear optics)

1987 Ph.D. (optics). Thesis: “Manifestation of infraand intermolecular interactions in vibrational spectra of some liquids”

2000 Dr.Sci. Thesis: “Physico-chemical mechanisms of biomolecular recognition”

2004 Professor (biophysics)

2006 Corresponding Member of NASU

Professional Employment:

1972–1976 Junior Research Scientist, Faculty of Radiophysics, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine

1976–1986 Research Scientist, Faculty of Radiophysics, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine

1987–1995 Senior Research Scientist, Department of Molecular Biophysics, Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

since 1995 Head of the Molecular Biophysics Department, IMBG NASU, Kyiv, Ukraine

1998, 2001 Professor-researcher, Department of Chemistry, Jackson State University, Jackson, MS, USA

Since 1999 Professor of the National University of “Kyiv-Mohyla Academy”, Chair of Physics and Mathematics, Kyiv, Ukraine

since 2003 Professor of Taras Shevchenko National University of Kyiv, Chair of Medical Radiophysics, Kyiv, Ukraine

since 2003 Deputy Director in Scientific Work, IMBG NASU, Kyiv, Ukraine

Membership:

Member of FEBS (Federation of European Biochemical Societies)

Member of Ukrainian Biochemical Society

Member of Ukrainian Biophysical Society

Member of Ukrainian Society of Molecular Biology

Associate Editor of Journal “Biopolymers and Cell”

Editorial Board member of Journal “Physics of the Alive” (Ukraine)

Editorial Board member of Journal “Ukrainica Bioorganica Acta” (Ukraine)

Honours, Prizes, Awards:

1994–1995 Soros International Science Foundation Grant

2003 Diploma of Verhovna Rada of Ukraine

2008 State Prize of Ukraine in Science and Technology

2008 Gershenson Award of National Academy of Sciences of Ukraine

2012 Honoured Worker of Science and Technology of Ukraine

Research Area:

Search for universal physical and chemical fundamentals of specific interactions between components of nucleoprotein complexes and elucidation of a role of prototropic tautomerism of nucleic acid bases and proton transfer in elementary processes of protein-nucleic acid recognition and interactions between bases in nucleic acids

An application of the methods of computational biology to the predictions of the properties of DNA and its components

Current Research Activities and Recent Achievements:

Using the methods of molecular spectroscopy (IR, UV, Raman, NMR) and quantum-chemical calculations at different levels of theory, the shifts in tautomeric equilibrium of nucleotide bases influenced by hydrogen bonding or interaction with ligands of peptidic nature and coordination with alkali cations are being investigated (Fig. 1, 2).

Fig. 1. Ura (Thy) tautomer double complexes with CH3COO. ΔG: Gibbs energy values of the complexes. Dotted lines show H-bonds, with their lengths presented in Å; the arrow means proton transfer
Fig. 2. Triple complexes of Ura (Thy) tautomers with CH3COO and Na+. ΔG: Gibbs energy values of the triple complexes. The bold dotted lines show H-bonds, with their lengths presented in Å; the arrows mean proton transfer

Changes in the tautomeric state of nucleotide bases, expected under the influence of heterogeneous environment in cells, may be regarded as one of possible mechanisms responsible for structural-dynamic transformations in protein-nucleic acid complexes. Theoretical and experimental investigations of the tautomeric state of nucleotide bases in model complexes of protein-nucleic recognition provide grounds to the concept of a significant role of the high-energy tautomers in biochemical processes.

The specific features of the spatial organisation of signal elements in cellular and viral RNAs, namely, their secondary and tertiary structures, are being studied using modern methods of electrophoresis, protonic buffer capacity, molecular modelling and bioinformatics.

A new line of investigation in the Department is directed to design, synthesis and study of biologically active heterocyclic compounds – antibacterial, antiviral and antitumor agents, which are inhibitors of the DNA and RNA polymerases and topoisomerases I and II. For screening inhibitors of the DNA and RNA polymerases there were applied effective and universal models: PCR and transcriptional complex of the phage T7 RNA polymerase. The cross-analysis procedure of the database of potential biological targets for low-molecular ligands is being used both to determine pharmacological profile of compounds and to search for the highest possible number of their targets. (Fig. 3)

Fig. 3. Inhibition by Acridone derivatives activity of (a) T7 RNA polymerase, (b) influenza virus neuraminidase, (c, d) HCV NS3 Helicase

In the Department there was invented a new method of the special spectroscopic technique ATR IR – attenuated total reflection of infrared light, covered by the patent of Ukraine. This technique can be used to obtain highquality IR spectra of fine films of nucleic acids and their complexes.

Based on quantum chemical calculation, the CH…O/N intermolecular hydrogen bonds in biologically significant canonical and modified pairs of DNA were investigated; there were proposed new structural mechanisms of spontaneous errors of insertion and the DNA replication errors, which are grounded on the Watson-Crick tautomeric hypothesis (Fig. 4).

Fig. 4. Hydrogen bonds in Watson-crick nucleoside pairs, corresponding to the AI and BI forms of DNA

In the frame of fundamental problems in the up-to- date phytobiology, the mechanisms of plants’ response to abiotic factors are being studied at the level of a genome reaction. Monitoring the global dynamics of the plant genome activity under the influence of chemical agents is being implemented by the DNA : RNA ratio lurking. This allows us to isolate molecules of genomic DNA of various functional activities with the purpose of studying their adequate structural changes.

Application of the state of the art methods of quantum chemistry to study tautomerization mechanisms of DNA bases.

Application of docking and molecular dynamics methods (both classical and ab initio) to study physical and chemical properties of nucleoside-tri-phosphates and their correct and incorrect interaction with active sites of DNA-polymerase.

National Grants:

Projects of National Academy of Sciences of Ukraine:

  • 2012–2016 Project: “Structural and functional genomics in the study of disorders in functioning viruses, bacteria and higher eukaryotes. CESSHIV-1 database as an instrument of investigating the secondary structure of control elements of human immunodeficiency virus” (scientific supervisor – D. M. Hovorun)
  • 2011 Grant of NASU for Young Scientists: “Conformational analysis of nucleic acid constituents as a key to understanding their biological activity” (scientific supervisor – Ye. P. Yurenko)
  • 2008–2009 NASU-STCU (National Academy of Sciences of Ukraine and Science and Technology Center in Ukraine) Project: “The RNA secondary structure role in HIV-1 replication: study by molecular genetics, phylogeny, and bioinformatics”
  • 2008 N 10 Project: “Phylogenetic study of structural variants of signaling elements in 5’ UTR of the HIV-1 genome”
  • 2007–2011 N 2.2.4.20 Project: “Investigation of the control elements structure in genome RNA of human immunodeficiency virus”
  • 2007–2009 Project: “Amides of triazinyl-propane carbonic acid – efficient inhibitors of human mycoses and mycotoxicoses: toxic and pharmacological studies and search for medical forms” (scientific supervisor – L. G. Palchykovska)
  • 2005–2007 Project: “Highly efficient inhibitors in fighting agents of human mycoses and mycotoxicoses on the basis of substituted amides of triazinyl-propane carbonic acid” (scientific supervisor – L. G.Palchykovska)

National Grants:

Projects of Ministry of Education and Science of Ukraine:

  • 2009–2010 The French-Ukrainian joint action program in the field of scientific and technological cooperation “Dnipro” CNRS, N Ì/111–2009 Project: “Investigation of tautomeric and conformational states of nucleotide bases and their nucleosides in model complexes of protein-nucleic acid recognition” (scientific supervisor – D. M. Hovorun)

Projects of State Fund for Fundamental Researches. During last decades we have received several SFFR grants, last of them:

  • 2011–2012 Project: “Conformational variability of 2’-deoxyribonucleosides and 2’-ribonucleosides: quantumchemical studies” (scientific supervisor – D. M. Hovorun)
  • 2011 N F 40/52-2011 Project: "Theoretical studies of biologically relevant molecular systems in the framework of continuous environment model, taking into account its heterogeneity" (scientific supervisor – L. G. Horb)

International Grants:

  • Research Partnership Program of STCU and EU N 4302 Project. Laboratory of Lymphotropic Viruses, D. I. Ivanovsky Institute of Virology of Russian Academy of Medical Sciences (scientific supervisor – D. M. Hovorun)

Selected publications:

  1. Glushenkov AN, Hovorun DM. Can nucleobase pairs offer a possibility of a direct 3D self-assembly? Nanoscale Res. Lett. 2016, 11(1):134. doi: 10.1186/s11671-016-1347-3.
  2. Sviatenko, L.K., Gorb, L., Hill, F.C., Leszczynska, D., Shukla, M.K., Okovytyy, S.I., Hovorun, D., Leszczynski, J. In Silico Alkaline Hydrolysis of Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine: Density Functional Theory Investigation. Environmental Science and Technology. 2016, 50(18):10039-10046.
  3. Brovarets’ O.O., Pérez-Sánchez H.E., Hovorun D.M. Structural grounds for the 2-aminopurine mutagenicity: A novel insight into the old problem of the replication errors. RSÑ Adv. 2016, 6(101): 99546-99557.
  4. T. Yu. Nikolaienko, L. A. Bulavin, D. M. Hovorun. Can we treat ab initio atomic charges and bond orders as conformation-independent electronic structure descriptors? RSC Adv. 2016, 6(78):74785-74796.
  5. Brovarets’ OO, Hovorun DM. The physicochemical essence of the purine•pyrimidine transition mismatches with Watson-Crick geometry in DNA: A•C* versa A*•C. A QM and QTAIM atomistic understanding. J. Biomol. Struct. & Dynam. 2015;33(1):28-55.
  6. Brovarets’ OO, Hovorun DM. Tautomeric transition between wobble À•Ñ DNA base mispair and Watson-Crick-like A•C* mismatch: miscrostructural mechanism and biological significance. Phys. Chem. Chem. Phys. 2015;17(23):15103-15110.
  7. Brovarets’ OO, Hovorun DM. How do long improper purine-purine pairs of DNA bases adapt their enzymatically competent conformation? Structural mechanism and its quantum-mechanical grounds. Ukr. J. Phys. (Special Issue devoted to Acad. L.A. Bulavin). 2015;60(8):748-756.
  8. Brovarets’ OO, Hovorun DM. A novel conception for spontaneous transversions caused by homo-pyrimidine DNA mismatches: A QM/QTAIM highlight. Phys. Chem. Chem. Phys. 2015;17(33):21381-21388.
  9. Brovarets’ OO, Hovorun DM. Novel physico-chemical mechanism of the mutagenic tautomerisation of the Watson-Crick-like A•G and C•T DNA base mispairs: a quantum-chemical picture. RSÑ Adv. 2015;5(81):66318-66333.
  10. Kolomiets IN, Zarudnaya MI, Potyahaylo AL, Hovorun DM. Structural insight into HIV-1 reverse transcription initiation in MAL-like templates (CRF01_AE, subtype G and CRF02_AG). J. Biomol. Struct. Dyn. 2015;33(2):418-433.
  11. Alexeeva I, Nosach L, Palchykovska L, Usenko L, Povnitsa O. Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues. Nucleosides, Nucleotides and Nucleic Acids. 2015;34:565–578.
  12. Zahanich I, Kondratov I, Naumchyk V, Kheylik Yu, Platonov M, Zozulya S, Krasavin M. Phenoxymethyl 1,3-oxazoles and 1,2,4-oxadiazoles as potent and selective agonists of free fatty acid receptor 1 (GPR40). Bioorganic & medicinal chemistry letters. 2015;25(6):3105-3111.
  13. Zubatiuk T, Shishkin O, Gorb L, Hovorun D, Leszczynski J. Structural Waters in the Minor and Major Grooves of DNA–A Major Factor Governing Structural Adjustments of the A−T Mini-Helix. J. Phys. Chem. B. 2015;119(2):381−391.
  14. Zubatiuk T, Kukuev M, Korolyova A, Gorb L, Nyporko A, Hovorun D, Leszczynski J. Structure and Binding Energy of Double-Stranded A-DNA Mini-helices: Quantum-Chemical Study. J. Phys. Chem. B. 2015;119(40):12741–12749.
  15. Leonid Gorb, Victor Kuz'min, Eugene Muratov. Application of Computational Techniques in Pharmacy and Medicine. Springer. 2014;Ð:550.
  16. Zarudnaya MI, Potyahaylo AL, Kolomiets IM, Hovorun DM. Phylogenetic study on structural elements of HIV-1 poly(A) region. 2. USE domain and TAR hairpin. Biopolym. Cell. 2014; 30(1):29-36.
  17. Kolomiets IN, Zarudnaya MI, Potyahaylo AL, Hovorun DM. Structural insight into HIV-1 reverse transcription initiation in MAL-liketemplates (CRF01_AE, subtype G and CRF02_AG). J. Biomol. Struct. Dyn. 2014; Epub ahead of print, Feb 21.
  18. Hurmach V. V., Balinskyi O. M., Platonov M. O., et al. Design of potentially active ligands for SH2 domains by molecular modeling methods. Biopolym. Cell. 2014;30(4):321-325.
  19. Ammosova T, Platonov M, Ivanov A, et al. 1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription. British Journal of Pharmacology. 2014;171:5059–5075.
  20. Paytakov G, Gorb L, Stepanyugin A, et al. Homodimers of cytosine and 1-methylcytosine. A DFT study of geometry, relative stability and H-NMR shifts in gas-phase and selected solvents. Journal of Molecular Modeling. 2014;20:2115-2119.
  21. Sviatenko LK, Gorb L, Hovorun D, Leszczynski J. In Silico kinetics and mechanism of interaction of cis-2-butene-1,4-dial with 2′-deoxycytidine. Chem Res Toxicol. 2014;27(6):981-9.
  22. Brovarets’ OO, Hovorun DM. Why the tautomerization of the G•C Watson-Crick base pair via the DPT does not cause point mutations during DNA replication? QM and QTAIM comprehensive analysis. Journal of Biomolecular Structure & Dynamics. 2014;32:1474-1499.
  23. Brovarets'OO, Zhurakivsky RO, Hovorun DM. Is the DPT tautomerisation of the long A•G Watson-Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question. Journal of Computional Chemistry. 2014;35:451-466.
  24. Brovarets’ OO, Zhurakivsky RO, Hovorun DM. Does the tautomeric status of the adenine bases change under the dissociation of the À*•Àsyn Topal-Fresco DNA mismatch? A combined QM and QTAIM atomistic insight. Physical Chemistry Chemical Physics. 2014;16:3715-372.
  25. Brovarets’ OO, Zhurakivsky RO, Hovorun DM. Structural, energetic and tautomeric properties of the T•T*/T*•T DNA mismatch involving mutagenic tautomer of thymine: A QM and QTAIM insight. Chemical Physics Letters. 2014;592:247-255.
  26. Brovarets'OO, Zhurakivsky RO, Hovorun DM. A QM/QTAIM microstructural analysis of the tautomerisation via the DPT of the hypoxanthine•adenine nucleobase pair. Molecular Physics. 2014;112:2005-2016.
  27. Nikolaienko TYu, Bulavin LA, Hovorun DM. JANPA: An open source cross-platform implementation of the Natural Population Analysis on the Java platform. Theoretical and Computational Chemistry. 2014; DOI: 10.1016/j.comptc.2014.10.002.
  28. Zarudnaya MI, Potyahaylo AL, Kolomiets IM, Hovorun DM. Phylogenetic study on structural elements of HIV-1 poly(A) region. 1. PolyA and DSE hairpins. Biopolym. Cell. 2013; 29(6):454-462.
  29. Brovarets' OO, Yurenko YP, Hovorun DM. Intermolecular CH•••O/N Hbonds in the biologically important pairs of natural nucleobases: a thorough quantumchemical study. J Biomol Struct Dyn. 2013 Jun 03. doi:10.1080/07391102.2013.799439
  30. Zarudnaya MI, Potyahaylo AL, Kolomiets IM, Hovorun DM. Structural model of the complete poly(A) region of HIV­1 pre­ mRNA. J Biomol Struct Dyn. 2013;31(10):1044–1056. doi: 10.1080/07391102.2012.718530
  31. Ford­Green J, Isayev O, Gorb L, Perkins EJ, Leszczynski J. Evaluation of natural and nitramine binding energies to 3­D models of the S1S2 domains in the N­methyl­D­aspartate receptor. J Mol Model. 2012;18(4):1273–84. doi: 10.1007/s00894-011-1152-y
  32. Isayev O, Crespo­Hernandez CE, Gorb L, Hill FC, Leszczynski J. In silico structure­function analysis of E. cloacae nitroreductase. Proteins. 2012;80(12):2728–41. doi:10.1002/prot.24157
  33. Sviatenko L, Gorb L, Hovorun D, Leszczynski J. Interaction of 2'­deoxyadenosine with cis­2­butene­1,4­dial: computational approach to analysis of multistep chemical reactions. J Phys Chem A. 2012;116(9):2333–42. doi:10.1021/jp211911u
  34. Brovarets' OO, Yurenko YP, Dubey IY, Hovorun DM. Can DNAbinding proteins of replisome tautomerize nucleotide bases? Ab initio model study. J Biomol Struct Dyn. 2012;29(6):597–605. doi:10.1080/07391102.2011.672624
  35. Shishkin OV, Dopieralski P, Omelchenko IV, Gorb L, Latajka Z, Leszczynski J. Dynamical Nonplanarity of Benzene. Evidences from the Car–Parrinello Molecular Dynamics Study. J. Phys. Chem. Lett. 2011;2(22):2881–4. doi: 10.1021/jz201327t
  36. Yurenko YP, Zhurakivsky RO, Samijlenko SP, Hovorun DM. Intramolecular CH•••O hydrogen bonds in the AI and BI DNA­like conformers of canonical nucleosides and their Watson­Crick pairs. Quantum chemical and AIM analysis. J Biomol Struct Dyn. 2011;29(1):51–65. doi:10.1080/07391102.2011.10507374
  37. Furmanchuk A, Isayev O, Gorb L, Shishkin OV, Hovorun DM, Leszczynski J. Novel view on the mechanism of water­assisted proton transfer in the DNA bases: bulk water hydration. Phys Chem Chem Phys. 2011;13(10):4311–7. doi:10.1039/c0cp02177f
  38. Samijlenko SP, Yurenko YP, Stepanyugin AV, Hovorun DM. Tautomeric equilibrium of uracil and thymine in model protein­ nucleic acid contacts. Spectroscopic and quantum chemical approach. J Phys Chem B. 2010;114(3):1454–61. doi: 10.1021/jp909099a
  39. Danilov VI, van Mourik T, Kurita N, Wakabayashi H, Tsukamoto T, Hovorun DM. On the mechanism of the mutagenic action of 5­bromouracil: a DFT study of uracil and 5­bromouracil in a water cluster. J Phys Chem A. 2009;113(11):2233–5. doi: 10.1021/jp811007j
  40. De Logu A, Palchykovska LH, Kostina VH, et al. Novel N­aryl­and N­heteryl phenazine­1­carboxamides as potential agents for the treatment of infections sustained by drug­resistant and multidrug­resistant Mycobacterium tuberculosis. Int J Antimicrob Agents. 2009;33(3):223–9. doi:10.1016/j.ijantimicag.2008.09.016
  41. StankiewiczDrogon A, Palchykovska LG, Kostina VG, Alexeeva IV, Shved AD, BoguszewskaChachulska AM. New acridone4carboxylic acid derivatives as potential inhibitors of hepatitis C virus infection. Bioorg. Med. Chem. 2008; 6(19):8846–8852. doi:10.1016/j.bmc.2008.08.074
  42. Zarudnaya MI, Kolomiets IM, Potyahaylo AL, Hovorun DM. Downstream elements of mammalian pre­mRNA polyadenylation signals: primary, secondary and higher­order structures. Nucleic Acids Res. 2003;31(5):1375–86. doi: 10.1093/nar/gkg241
  43. Cherepenko E. I.; Molecular mechanisms of cell protection and pharmacotherapy. (in Russian). – Kyiv. Naukova dumka, 2012. – 260 p. – ISBN 978-966-00-1264-6.