Prediction of protein-ligand binding sites modulating activity of MAST protein kinases

  • P. A. Karpov Institute of Food Biotechnology and Genomics NAS of Ukraine, Ukraine, 04123, Kyiv, Baidy Vyshnevetskoho str., 2A https://orcid.org/0000-0002-6876-642X
  • A. O. Steshenko Institute of Food Biotechnology and Genomics NAS of Ukraine, Ukraine, 04123, Kyiv, Baidy Vyshnevetskoho str., 2A; Educational Scientific Center "Institute of Biology and Medicine" of Taras Shevchenko National University of Kyiv, Ukraine, 03022, Kyiv, acad. Glushkov ave., 2
  • S. P. Ozheredov Institute of Food Biotechnology and Genomics NAS of Ukraine, Ukraine, 04123, Kyiv, Baidy Vyshnevetskoho str., 2A https://orcid.org/0000-0003-4710-0706
  • Y. B. Blume Institute of Food Biotechnology and Genomics NAS of Ukraine, Ukraine, 04123, Kyiv, Baidy Vyshnevetskoho str., 2A https://orcid.org/0000-0001-7078-7548
DOI: https://doi.org/10.7124/FEEO.v35.1677
Keywords: MAST family, protein kinases, inhibitors, ligands, binding site

Abstract

Aim. Identification of the protein-ligand binding sites, that may be the target of compounds, affecting individual human protein kinases of the MAST family (MAST1, 2, 3, 4 and MASTL / GWL). Methods. Literature and database search. Comparison of protein and ligand structures. Protein structure modeling, structural superimposition, etc. Results. The structural alignment demonstrates significant similarity of catalytic domains in MAST1, 2, 3, 4 and MASTL (GWL). It justifies transferring of reference ligands from PDB structures to human MASTs, discovering potential sites of ligand binding. 13 sites of ligand-binding were specified based on refrence ligands, transferred from RCSB Protein Data Bank structures, and differences in sites amino acid composition of MAST family members were discovered. Сonclusions. Based on the differences in the amino acid composition of the studied pockets in MAST1, 2, 3, 4 and MASTL (GWL), the sites B, C, D, E, F, were selected for further study and virtual screening for new selective inhibitors of individual members of MAST protein kinase family.

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