Pracownie badawcze

Prof. dr hab. Piotr Zielenkiewicz

Zakład Bioinformatyki

Zakres badań

Our laboratory applies in silico approaches to address molecular biology problems.

Badania

Najważniejsze osiągnięcia badawcze

  • We established the general methodology for the construction of protein-protein interaction peptide inhibitors and successfully applied it to a number of biologically meaningful examples.
  • We discovered novel potent deltaF508-CFTR correctors as potential drugs against Cystic Fibrosis (CF)
  • We proposed a comprehensive, genome-wide model of translation.
  • We described the role of plant miRNAs in the antiinflammatory properties of selected edible plants.

Opis badań

Scientific interests of our laboratory include, but are not limited to:

  • Protein-protein recognition and the design of protein-protein interaction inhibitors.
  • Macromolecular crowding.
  • Modeling and modifying the regulation of basic cellular processes and metabolic pathways.
  • Protein modeling.
  • Analyses of genome sequence data (particularly in the context of phylogenetic analysis).
  • Development of drug design methodologies.
  • Analyses of protein interaction networks.
  • Literature mining.

Metodologia

In our laboratory, we use software tools for:

  • Sequence and structure analysis (e.g., EMBOSS).
  • Visualization and structure modeling (e.g., Chimera, YASARA, Swiss-PDBViewer).
  • Pathway and metabolic pathway modeling and analysis (e.g., Cytoscape, IPA, Gepasi)
  • Docking (e.g., DOCK).
  • Molecular dynamics (e.g., AMBER, GROMACS).
  • Home-developed tools (e.g., kalasanty, pafnucye, plec, oddt, transimulation, ht-sas, elise, tools4mirs).

Our HPC infrastructure is built around HP blade servers with Intel Xeon X5650 6-core processors and AMD Opteron 6174 12-core processors. Each core has 2 MB of RAM. The servers are diskless and connected with a high speed (32 Mb/s) InfiniBand QDR40 connection. This interconnect provides direct memory access and enables ultra-low latency between computing nodes. The infrastructure consists of 32 Intel-based servers and 16 AMD servers, for a total of 1152 cores. This environment is further enriched by 8 GPU Nvidia TESLA C2080 cards with 448 cores each. Storage is built around LustreFS, a special-purpose modular system that is designed for high I/O memory (6 rack servers, 72 Intel cores) and a HITACHI AMS2500 storage system with 0.5 PB of storage size. Additionally, five application servers provide virtualization capacities, with a total of 240 cores and 1 TB of RAM installed). Software that is used in this installation is almost exclusively free and open source stack (Linux, Torque, Maui, Xen, MySQL, Apache, and others). Altogether, our HPC environment is able to achieve over 40 Tflops.

Wybrane publikacje

  • Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain. Odolczyk N, Fritsch J, Norez C, Servel N, da Cunha MF, Bitam S, Kupniewska A, Wiszniewski L, Colas J, Tarnowski K, Tondelier D, Roldan A, Saussereau EL, Melin-Heschel P, Wieczorek G, Lukacs GL, Dadlez M, Faure G, Herrmann H, Ollero M, Becq F, Zielenkiewicz P, Edelman A. EMBO Mol Med. 2013 Oct;5(10):1484-501. doi: 10.1002/emmm.201302699.
  • A comprehensive, quantitative, and genome-wide model of translation. Siwiak M, Zielenkiewicz P. PLoS Comput Biol. 2010 Jul 29;6(7):e1000865. doi: 10.1371/journal.pcbi.1000865.
  • Mapping Protein-Protein Interactions of the Resistance-Related Bacterial Zeta Toxin-Epsilon Antitoxin Complex (ε₂ζ₂) with High Affinity Peptide Ligands Using Fluorescence Polarization. Fernández-Bachiller MI, Brzozowska I, Odolczyk N, Zielenkiewicz U, Zielenkiewicz P, Rademann J. Toxins (Basel). 2016 Jul 16;8(7):222. doi: 10.3390/toxins8070222.

Współpraca

  • Joerg Rademann, Freie Universitaet Berlin, D
  • Aleksander Edelman, INSERM, FR
  • Sarah Reece, Edinburgh University, UK
  • Chris Janse, Leiden University, NL
  • Wolfram Saenger, Freie Universitaet Berlin, D
  • Grażyna Faure-Kuźmińska, Institute Pasteur, Paris, France
  • Stephanie Trudel, Universitaire Amiens Picardie, Amiens, France

Publikacje (z afiliacją IBB PAN)

SOBIEŚCIAK T.D., ZIELENKIEWICZ P., Non-specific clustering of histidine tagged green fluorescent protein mediated by surface interactions: the collective effect in the protein-adsorption behaviour. RSC Advances (2013) 3: 10479-10486 IF 2.562
GŁADKI A., KACZANOWSKI S., SZCZĘSNY P., ZIELENKIEWICZ P., The evolutionary rate of antibacterial drug targets. BMC Bioinformatics (2013) 14: 36 (10 p./electronic only) IF 3.024
PAWŁOWSKI P.H., KACZANOWSKI S., ZIELENKIEWICZ P., A kinetic model of the evolution of a protein interaction network. BMC Genomics (2013) 14: 172 (27 p.) IF 4.397
POZNAŃSKI J., SZCZĘSNY P., RUSZCZYŃSKA K., ZIELENKIEWICZ P., PĄCZEK L., Proteins contribute insignificantly to the intrinsic buffering capacity of yeast cytoplasm. Biochemical and Biophysical Research Communications (2013) 430(2): 741-744 IF 2.406
SIWIAK M., EDELMAN A., ZIELENKIEWICZ P., Structural models of CFTR-AMPK and CFTR-PKA interactions: R-domain flexibility is a key factor in CFTR regulation. Journal of Molecular Modeling (2012) 18(1):83-90 IF 1.797
SIWIAK M., ZIELENKIEWICZ P., A comprehensive, quantitative, and genome-wide model of translation. PLoS Computational Biology (2010) 6(7): e1000865 IF 5,759
SOBIEŚCIAK T.D., ZIELENKIEWICZ P., Double selective synthetic approach to the N-functionalized 1,4,7-triazacyclononane derivatives: chelating compounds for controllable protein orientation. Journal of Organic Chemistry (2010) 75(6): 2069-2072 IF 4,219
KACZANOWSKI S., ZIELENKIEWICZ P., Why similar protein sequences encode similar three-dimensional structures? Theoretical Chemistry Accounts (2010) 125: 643-650 IF 2,584
KACZANOWSKI S., SIEDLECKI P., ZIELENKIEWICZ P., The high throughput sequence annotation service (HT-SAS) - the shortcut from sequence to true Medline words. BMC Bioinformatics (2009) 10: 148 (7 p./electronic only) IF 3,781
TRZCIŃSKA-DANIELEWICZ J., BILSKA A., FRONK J., ZIELENKIEWICZ P., JAROCHOWSKA E., ROSZCZYK M., JOŃCZYK M., AXENTOWICZ E., SKONECZNY M., SOWIŃSKI P., Global analysis of gene expression in maize leaves treated with low temperature I. Moderate chilling (14 °C). Plant Science (2009) 177: 648-658 IF 1,974
PAWŁOWSKI P.H., BURZYŃSKA B., ZIELENKIEWICZ P., Theoretical model of thalassemic erythrocyte shape transformation. Journal of Theoretical Biology (2008) 254: 575-579 IF 2,323
WIECZOREK G., ZIELENKIEWICZ P., Influence of macromolecular crowding on protein-protein association rates - a brownian dynamics study. Biophysical Journal (2008) 95: 5030-5036 IF 4,757
WIECZOREK G., ZIELENKIEWICZ P., F508 mutation increases conformational flexibility of CFTR protein. Journal of Cystic Fibrosis (2008) 7: 295-300 IF 1,550
PAWŁOWSKI P.H., KACZANOWSKI S., ZIELENKIEWICZ P., Protein interaction network. Double exponential model. Journal of Proteomics & Bioinformatics (2008) 1(2): 061-067 IF-
GŁADKI A., SIEDLECKI P., KACZANOWSKI S., ZIELENKIEWICZ P., e-LiSe-an online tool for finding in the '(Medline) haystack'. Bioinformatics (2008) 24(8): 1115-1117 IF 5,039
WIECZOREK G., ZIELENKIEWICZ P., Using tetrahedral grid-based protein models in docking. Journal of Physics-Condensed Matter (2007) 19: 8pp BS http:www.iop.org/EJ/journal/JPhysCM IF 2,038
ORŁOWSKI J., KACZANOWSKI S., ZIELENKIEWICZ P., Overrepresentation of interactions between homologous proteins in interactomes. FEBS Letters (2007) 581: 52-56 IF 3,372
BURZA A.M., PĘKALA I., SIKORA J., SIEDLECKI P., MALAGOCKI P., BUCHOLC M., KOPER L., ZIELENKIEWICZ P., DADLEZ M., DOBROWOLSKA G., Nicotiana tabacum osmotic stress-activated kinase is regulated by phosphorylation on ser-154 and ser-158 in the kinase activation loop. Journal of Biological Chemistry (2006) 281: 34299-34311 IF 5,808
PAWŁOWSKI P.H., BURZYŃSKA B., ZIELENKIEWICZ P., Theoretical model of reticulocyte to erythrocyte shape transformation. Journal of Theoretical Biology (2006) 243: 24-38 IF 2,264
SIEDLECKI P., ZIELENKIEWICZ P., Mammalian DNA methyltransferases. Acta Biochimica Polonica (2006) 53: 245-256 IF 1,363

Zespół

Patenty

    • Compounds as modulators of a mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. ODOLCZYK, Norbert ; ZIELENKIEWICZ, Piotr; WIECZOREK, Grzegorz; EDELMAN, Aleksander; TONDELIER, Danielle; FRITSCH, Janine. US ( 2018) 10,398,665, ; US 10,420,738,; US 10,463,639
    • Use of a mir172 molecule for decreasing inflammation. Łukasik, Anna; Zielenkiewicz, Piotr; Szweykowska-Kulińska, Zofia; Paczek, Leszek; Nowaczyk, Maria. (2018) EP3035941