Laboratory of Computer Modeling

Laboratory of Computer Modeling performs rational design of enzyme inhibitors with the aid of molecular docking, molecular dynamics and pharmacophore modeling approaches using its own compounds collection containing about 150,000 drug-like small organic molecules which are immediately available for screening. Department has well equipped laboratories for chemical synthesis aimed at optimization of compounds activity, selectivity and ADME properties.

Research Services: 
  • Virtual high-throughput screening using structure-based (molecular docking) and ligand-based (QSAR, pharmacophore modeling) approaches;
  • Identification and analysis of binding sites;
  • Structure-activity relationship (SAR) analysis;
  • Computational studies of drug-receptor interactions;
  • Hit identification and optimization;
  • Hit to lead optimization;
  • In silico ADME predictions;
  • Molecular dynamics of proteins, nucleic acids, extra large heterogeneous systems;
  • Design of target-focused compound libraries with high affinity to the molecular targets (our compound collection contains about 200,000 organic compounds which are immediately available for screening).
  • Protein sequence analysis and alignment;
  • Homology modeling;
  • Protein modeling (variability analysis, structure analysis, modification analysis, fold recognition, secondary structure prediction, disorder region prediction, domain prediction, Ab Initio spatial structure prediction, spatial structure quality evaluation, spatial structure correction);
  • Nucleic acids modeling (DNA spatial structure prediction, RNA spatial structure prediction);
  • Accurate prediction of binding energy;
  • Systems network analysis;
  • Prediction of aptamer structure;
  • Prediction of biomolecular contact surfaces.
Area(s) of expertise: 

Laboratory of Computer Modeling develops molecular probes to discover and validate biological drug targets, enzyme inhibitors, biological receptor agonists and antagonists, performs molecular docking, pharmacophore modeling, molecular dynamics simulations, SAR studies.

Selected publications: 
  1. Gudzera OI, Golub AG, Bdzhola VG, Volynets GP, Lukashov SS, Kovalenko OP, Kriklivyi IA, Yaremchuk AD, Starosyla S.A., Yarmoluk S.M., Tukalo M.A. (2016) Discovery of potent anti-tuberculosis agents targeting leucyl-tRNA synthetase. doi:10.1016/j.bmc.2016.01.028
  2. Starosyla SA, Volynets GP, Lukashov SS, Gorbatiuk OB, Golub AG, Bdzhola VG, Yarmoluk SM (2015) Identification of apoptosis signal-regulating kinase 1 (ASK1) inhibitors among the derivatives of benzothiazol-2-yl-3-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one. Bioorg Med Chem 23(10):2489-2497.
  3. Guerra B, Bischoff N, Bdzhola VG, Yarmoluk SM, Issinger OG, Golub AG, Niefind K (2015) A note of caution on the role of halogen bonds for protein kinase/inhibitor recognition suggested by high- and low-salt CK2α complex structures. ACS Chem Biol 10(7):1654-1660.
  4. Gryshchenko AA, Bdzhola VG, Balanda AO, Briukhovetska NV, Kotey IM, Golub AG, Ruban TP, Lukash LL, Yarmoluk SM (2015) Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1. Bioorg Med Chem 23(9):2287-2293.
  5. Gryshchenko AA, Levchenko KV, Bdzhola VG, Ruban TP, Lukash LL, Yarmoluk SM (2015) Design, synthesis and biological evaluation of naphthostyril derivatives as novel protein kinase FGFR1 inhibitors. J Enzyme Inhib Med Chem 30(1):126-132.
Completed research contracts: 
  • Protein kinase inhibitors were developed for Adamed Company (Poland);
  • The methodologies for target-oriented screening of compounds with the aim of identification of potential antibacterial agents were developed for State Agency for Science, Innovation and Informatization of Ukraine;
  • Inhibitors of aminoacyl-tRNA synthetases with selective action against causative agent of tuberculosis were developed in the frame of STCU-NASU, Targeted Research and Development Initiatives Program;
  • Small-molecular inhibitors of protein kinases CK2, ASK1 and FGFR1 were designed in the frame of State Programs of the NAS of Ukraine.
Specialized labs and equipment: 

Name of equipment

Description of function

Computer cluster

38 processor cluster for computer-intensive jobs

Access to the cluster of the Institute of Molecular Biology and Genetics of the NAS of Ukraine (360 processors).

Computer Software

DOCK
AutoDock
Vina

Molecular docking

Pharmer
Pharmagist

Pharmacophore screening

Amber
GROMACS

Molecular mechanics and dynamics

Jchem
CheD

Compound collection analysis

Modeller

Homology modeling

Chimera
VEGA ZZ
PMV
DS Vizualizer

Visualization

Compound collection (about 150,000 compounds)

Library screening, drug discovery