Department of Molecular and Quantum Biophysics
Dmytro M. Hovorun
Professor, Dr. Sci. (Mol. Biol.),
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
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
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
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).
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)
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).
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.
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 188.8.131.52 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)
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)
- 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)
- H.H. Repich, V.V. Orysyk, L.G. Palchykovska, S.I. Orysyk, Yu.L. Zborovskii, O.V. Vasylchenko, O.V. Storozhuk, A.A. Biluk, V.V. Nikulina, L.V. Garmanchuk, V.I. Pekhnyo, M.V. Vovk. Synthesis, spectral characterization of novel Pd(II), Pt(II) -coordination compounds based on N-allylthioureas. Cytotoxic properties and DNA binding ability. J. of Inorganic Biochemistry. – 2017. – v168. – P. 98–106
- Gorb, L., Zubatiuk, T.A., Zubatyuk, R., Hovorun, D., Leszczynski, J. d(A)3d(T)3 and d(G)3d(C)3 B-DNA mini-helixes: the DFT/M06-2x and DFT/B97-D3 comparison of geometrical and energetic characteristics. Journal of Molecular Modeling 23 (10), 289-298, 2017
- Zarudnaya M. I., Potyahaylo A. L., Hovorun D. M. Dependence of DNA persistence length on ionic conditions. Biopolymers and Cell. –2017. – Vol. 33, N 2. – P. 81-91. doi:10.7124/bc.000946
- Gooch, A., Sizochenko, N., Sviatenko, L., Gorb, L., Leszczynski, J. A quantum chemical based toxicity study of estimated reduction potential and hydrophobicity in series of nitroaromatic compounds. SAR and QSAR in Environmental Research 28(2), pp. 133-137, 2017
- Sviatenko, L.K., Gorb, L., Leszczynska, D., Okovytyy, S.I., Shukla, M.K., Leszczynski, J. In silico kinetics of alkaline hydrolysis of 1,3,5-trinitro-1,3,5-triazinane (RDX): M06-2X investigation. Environmental science. Processes & impacts, 19(3), pp. 388-392, 2017
- Brovarets’ O.O., Voiteshenko, I.S., Pérez-Sánchez H.E., & Hovorun D.M. A QM/QTAIM research under the magnifying glass of the DPT tautomerisation of the wobble mispairs involving 2-aminopurine New Journal of Chemistry. – 2017. – DOI: 10.1039/C7NJ00717E
- Brovarets’ O.O., Voiteshenko, I.S, Pérez-Sánchez H.E., & Hovorun D.M. A QM/QTAIM detailed look at the Watson-Crick↔wobble tautomeric transformations of the 2-aminopurine•pyrimidine mispairs Journal of Biomolecular Structure & Dynamics. – 2017. – DOI: 10.1080/07391102.2017.1331864
- Brovarets’ O.O., Voiteshenko, I.S., & Hovorun D.M. Physico-chemical profiles of the wobble↔Watson-Crick G*•2AP(w)↔G•2AP(WC) and A•2AP(w)↔A*•2AP(WC) tautomerisations: A QM/QTAIM comprehensive survey. Physical Chemistry Chemical Physics. – 2017. Crossref DOI link: https://doi.org/10.1039/C7CP05139E
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Leonid Gorb, Victor Kuz'min, Eugene Muratov. Application of Computational Techniques in Pharmacy and Medicine. Springer. 2014;Ð:550.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Cherepenko E. I.; Molecular mechanisms of cell protection and pharmacotherapy. (in Russian). – Kyiv. Naukova dumka, 2012. – 260 p. – ISBN 978-966-00-1264-6.