Department of Protein Engineering and Bioinformatics

Head

Olexander I. Kornelyuk

Professor, Dr. Sci. (Mol. Biol.),
Corresponding Member of NASU
Phone: (380-44) 526-55-89;
Fax: (380-44) 526-07-59;
E-mail: kornelyuk@imbg.org.ua

Group of Modification of Biologically Active Compounds

Head: Anatoliy I. Potopalsky
MD, Senior Lecturer

Education and Degrees:

19671972 Graduate Student, Faculty of Radiophysics, V. N. Karazin Kharkiv National University, Kharkiv, Ukraine, M.Sc. (biophysics)

1981 Ph.D. (molecular biology), Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

1995 Dr.Sci. (molecular biology), IMBG NASU, Kyiv, Ukraine

1999 Professor (molecular biology)

2006 Corresponding Member of NASU

Professional Employment:

19721975 Engineer, Junior Research Scientist, B. Verkin Institute for Low Temperature Physics and Engineering, NASU, Kharkiv, Ukraine

19751978 Postgraduate Student, IMBG NASU, Kyiv, Ukraine

19781987 Junior Research Scientist, Senior Research Scientist, Department of Structure and Functions of Nucleic Acid, IMBG NASU, Kyiv, Ukraine

19822004 Professor, Department of Molecular Biology, Faculty of Biology, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine

19872000 Deputy Head of the Department, Group Leader, Department of Structure and Function of Nucleic Acids, IMBG NASU, Kyiv, Ukraine

Since 2001 Head of the Department of Protein Engineering, IMBG NASU, Kyiv, Ukraine

Since 2008 Professor, Head of the Division of Molecular Biology, Biophysics and Biotechnology, Institute of High Technologies, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine

Membership:

Member of the Ukrainian Biochemical Society

Member of the Ukrainian Biophysical Society

Member of Scientific Council of the IMBG NASU

Since 1996 Member of the New York Academy of Sciences

Honours, Prizes, Awards:

2003 Diploma of Honour and valuable gift from Mayor of Kyiv

2006 Diploma of Honour from Ministry of Education and Science of Ukraine

2008 State Prize of Ukraine in Science and Technology

2010 Diploma of the Verkhovna Rada of Ukraine

2012 Diploma of the best lecturer of the Institute of High Technologies of Taras Shevchenko National University of Kyiv

2013 Komisarenko Award of National Academy of Sciences of Ukraine

Research Area:

Molecular mechanisms of aminoacyl-tRNA synthetases and the functional role of protein dynamics

Computational modeling of protein structure

Molecular dynamics simulations of proteins and proteinnucleic acid complexes

Grid technologies in molecular biology

urrent Research Activities and Recent Achievements:

Molecular dynamics simulations of proteins.

Molecular dynamics simulation (MD) is a very important approach of structural bioinformatics due to the possibility of modeling of proteins and their complexes in solution. However, MD simulations are computationally very expensive and usually require a high processing power and huge storage space for trajectories. Grid computing is a very promising approach in order to encounter the limits of computational power of long MD simulations. Recently, in our department an all-atom model of full-length Hs tyrosyl-tRNA synthetase (TyrRS) was developed [1]. Long 100 ns MD simulations in grid of HsTyrRS (Fig. 1A). Domain binding interfaces also revealed the formation of H-bonds between ELR cytokine motif in TyrRS and its protection by C-module (Fig. 1B) [1].

Fig. 1. Asymmetric structure and domain binding interfaces of human tyrosyl-tRNA synthetase after 100 ns molecular dynamics simulation (A). Typical configuration of the hydrogen bonds between the ELR cytokine motif of N-module and the C-module at simulation time of 96 ns (B)
Virtual laboratory MolDynGrid.

MolDynGrid virtual laboratory (http://moldyngrid.org) was established for interdisciplinary studies in computational structural biology and bioinformatics (Fig. 2). The main objective of MolDynGrid project was to provide an effective infrastructure for automation of MD simulatons and trajectory analysis in Grid environment. Since 2013 Virtual Organization moldyngrid is a part of European Grid infrastructure and utilize LRZ Linux cluster resources in Germany (Fig. 2).

Fig. 2. Virtual Laboratory MolDynGrid as a part of Ukrainian National Grid-infrastructure (UNG) was established for interdisciplinary research in computational structural biology and bioinformatics. MolDynGrid usually utilizes computing elements (CE) of 8 clusters and storage elements (SE) of 2 clusters that correspond to ~2500 CPUs and ~100 TBytes of disk space, respectively)
MD simulations of HsTyrRS mutants associated with Charcot-Marie-Tooth disease.

Several missence mutations G41R, E196K and 153-156delVKQV in were identified in families with CMT disease. MD simulations of CMT HsTyrRS mutants were performed in 100 ns time interval using MolDynGrid virtual laboratory services. A local β-sheet formation was observed in Rossmann fold insertion region in all 3 mutants (Fig. 3). Dispersion of CMT mutations in HsTyrRS could be understood in terms of long-range structural effects on dimer interface.

Fig. 3. Local β-sheet formation in K147-E157 region for 20-100 ns MD simulation time interval of in G41R mutant of H.sapiens TyrRS at Charcot-Marie-Tooth disease)
Solution structure of EMAP II cytokine.

Solution structure of a novel EMAP II cytokine was determined by multidimentional NMR spectroscopy in collaboration with Institute of Biochemistry and Biophysics in Warsaw (Fig. 4). Solution structure of EMAP II cytokine revealed more exposed cytokine motif at N-terminal β-strand and highly flexible RNA binding surface.

Fig. 4. Solution 3D structure of human EMAP II cytokine as determined by multidimentional NMR spectroscopy (A). Backbone view of ensemble of 20 low energy structures (B))
Nanocomposite antitumor complexes of of EMAP II cytokine.

Fundamentals of a new technology of antitumor of EMAP II cytokine production were developed in our department. EMAP II cytokine revealed antitumor activity on the growth of carcinoma of human prostate (Patent of Ukraine #33215). A novel nanocomposite complexes of EMAP II cytokine were proposed as novel anticancer drug (Patent of Ukraine #64374).

National Grants:

Projects of the National Academy of Sciences of Ukraine:

  • 20132015 N 49/2013 Project: Development of intelligent supercomputer systems of SKIT family, ensuring their effective functioning and development of information technology, advanced mathematics, hardware and software to solve complex and complicated scientific problems (Intelligence) (scientific supervisor Kornelyuk O. I.)
  • 20102014 N 34/2013 Project: Fundamentals of a new technology of antitumor cytokine EMAP II production and its mutant forms with enhanced antiangiogenic effect (scientific supervisor Kornelyuk O. I.)
  • 20092013 N 15/2013 Project: Design and implementation of computer services for the analysis of molecular dynamics of proteins in the virtual laboratory MolDynGrid and its integration into the European grid infrastructure (scientific supervisor Kornelyuk O. I.)

Collaboration:

with Ukrainian organizations:

  • Taras Shevchenko National University of Kyiv (Kyiv)
  • State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine (Kyiv)
  • O. V. Palladin Institute of Biochemistry, NASU (Kyiv)
  • National Technical University of Ukraine Kyiv Polytechnic Institute (Kyiv)

with foreign organizations:

  • International Institute of Molecular and Cell Biology (Warsaw, Poland)
  • Warsaw University, Chemistry Department (Warsaw, Poland)
  • Institute of Biochemistry and Biophysics, PAS (Warsaw, Poland)
  • Slovenian NMR Centre, National Institute of Chemistry (Ljubljana, Slovenia)

Selected publications:

  1. Kravchuk VO, Savytskyi OV, Odynets KO, Mykuliak VV, Kornelyuk AI. Computational Modeling and Molecular Dynamics Simulations of Mammalian Cytoplasmic Tyrosyl-tRNA Synthetase and Its Complexes with Substrates. J Biomol Struct Dyn. 2016, 11:1-42.
  2. Babichev S. A., Kornelyuk A. I., Lytvynenko V. I., Osypenko V. V.Computational analysis of microarray gene expression profiles of lung cancer Biopolym. Cell. 2016, 32(1):70-79.
  3. Vorobyova N, Lozhko D, Zhukov I, Kornelyuk A. Bacterial expression and isotope labeling of AIMP1/p43 codosome protein for structural studies by multidimensional NMR spectroscopy. Biopolymers & Cell. 2015;31(2):109-114.
  4. Grom MYu, Yakovenko LF, Granich VM, Dobrohod AS, Torbas OO, Radchenko A, Sirenko YuM, Sidorik LL, Kornelyuk AI. Autoantibodies against tyrosyl-tRNA synthetase and its separated domains at essential hypertension. Biopolymers & Cell. 2015;31(4):255-263.
  5. Mykuliak V, Dragan A, Kornelyuk A. Structural states of flexible catalytic loop of M. tuberculosis tyrosyl-tRNA synthetase in different enzyme-substrate complexes. Eur. Biophys J. Published online. 6 November 2014.
  6. Mykuliak V, Kornelyuk A. The mechanisms of substrates interaction with the active site of Mycobacterium tuberculosis tyrosyl-tRNA synthetase studied by molecular dynamics simulations. Biopolymers & Cell. 2014;30(2):157-162.
  7. K.V. Kotsarenko K, Lylo V, Ruban T,... A.I. Kornelyuk, et al. Influence of IFN-α2b and EMAP II and their medicinal forms on the MGMT gene expression in human cell lines. Biopolymers & Cell. 2014;30(6).
  8. Savytskyi OV, Yesylevskyy SO, Kornelyuk AI. Asymmetric structure and domain binding interfaces of human tyrosyltRNA synthetase studied by molecular dynamics simulations. J Mol Recognit. 2013;26(2):11320. doi:10.1002/jmr.2259
  9. Lozhko D, Stanek J, Kazimierczuk K, et al. (1)H, (13)C, and (15)N chemical shifts assignments for human endothelial monocyteactivating polypeptide EMAP II. Biomol NMR Assign. 013;7(1):259. doi:10.1007/s12104-012-9369-y
  10. A method of modeling antitumor effect on prostate adenocarcinoma, Patent of Ukraine, N 70342 from 11.06.2012.
  11. Reznikov AG, Chaykovskaya LV, Polyakova LI, Kornelyuk AI, Grygorenko VN. Cooperative antitumor effect of endothelialmonocyte activating polypeptide II and flutamide on human prostate cancer xenografts. Exp Oncol. 2011;33(4):2314.
  12. Yesylevskyy SO, Savytskyi OV, Odynets KA, Kornelyuk AI. Interdomain compactization in human tyrosyltRNA synthetase studied by the hierarchical rotations technique. Biophys Chem. 2011;154(23):908. doi:10.1016/j.bpc.2011.01.005
  13. Nanocomposite anticancer drug, Patent of Ukraine N 64374 from 14.11.2011.
  14. Salnikov A, Sliusar I, Sudakov O, Savytskyi O, Kornelyuk A. Virtual laboratory MolDynGrid as a part of scientific infrastructure for biomolecular simulations. International Journal of Computing.2010;9(4):295301
  15. Application of cytokinelike polypeptide EMAPII as a tool that shows antitumor activity on the growth of carcinoma of the human prostate, Patent of Ukraine N 33215 from 19.02.2008.
  16. Kordysh M, Kornelyuk A. Conformational flexibility of cytokinelike Cmodule of tyrosyltRNA synthetase monitored by Trp144 intrinsic fluorescence. J Fluoresc. 2006;16(5):70511. doi:10.1007/s10895-006-0113-9
  17. Kovalskyy D, Dubyna V, Mark AE, Kornelyuk A. A molecular dynamics study of the structural stability of HIV1 protease under physiological conditions: the role of Na+ ions in stabilizing the active site. Proteins. 2005;58(2):4508. doi:10.1002/prot.20304