Ukr.Biochem.J. 2015; Volume 87, Issue 1, Jan-Feb, pp. 109-120

doi: https://doi.org/10.15407/ubj87.01.109

Application of the methods of molecular modeling to the search for new biologically active substances

20.05.2015   Uncategorized   No comments

V. V. Hurmach1, O. M. Balinskyi1, M. O. Platonov2, O. M. Boyko1, Yu. I. Prylutskyy1

1Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: gyrmach@gmail.com;
2Institute of Molecular Biology and Genetics,
National Academy of Sciences of Ukraine, Kyiv

The searching for new chemical compounds possessing specific biological activity is a complex problem that needs the usage of modern methods of molecular modeling. In particular, for the prupose of searching for potentially active compounds for whole class of SH2 domains, a comparison of all available structures, their cluster analysis, molecular docking, selection of all possible pharmacophore models and GTM prediction were done. Obtained results testify to the considerable variability of binding of SH2 domains.

Keywords: , , , ,

References:

  1. Claverie JM. Gene number. What if there are only 30,000 human genes? Science. 2001 Feb 16;291(5507):1255-7. PubMed
  2. Alm E, Arkin AP. Biological networks. Curr Opin Struct Biol. 2003 Apr;13(2):193-202. Review. PubMed
  3. Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668-74. PubMed
  4. Liu BA, Jablonowski K, Raina M, Arcé M, Pawson T, Nash PD. The human and mouse complement resource of SH2 domain proteins–establishing the boundaries of phosphotyrosine signaling. Mol Cell. 2006;22:851-868.
  5. Dominguez C, Boelens R, Bonvin AM. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. J Am Chem Soc. 2003 Feb 19;125(7):1731-7. PubMed
  6. Brovarets’ OO, Yurenko YP, Hovorun DM. The significant role of the intermolecular CH⋯O/N hydrogen bonds in governing the biologically important pairs of the DNA and RNA modified bases: a comprehensive theoretical investigation. J Biomol Struct Dyn. 2014 Oct 28:1-29. [Epub ahead of print] PubMed
  7. Pawson T, Gish GD, Nash P. SH2 domains, interaction modules and cellular wiring. Trends Cell Biol. 2001 Dec;11(12):504-11. Review. PubMed
  8. Huang H, Li L, Wu C, Schibli D, Colwill K, Ma S, Li C, Roy P, Ho K, Songyang Z, Pawson T, Gao Y, Li SS. Defining the specificity space of the human SRC homology 2 domain. Mol Cell Proteomics. 2008 Apr;7(4):768-84. PubMed
  9. Silva CM. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene. 2004 Oct 18;23(48):8017-23. Review. PubMed
  10. Boyko YV, Vystoropsky OO, Nychy­poruk TV, Sudakov OO. Kyiv National Taras Shevchenko University High Performance Computing Cluster. Third International Young Scientists Conference on Applied Physics. 2003. P. 189-181.
  11. Chuprina A, Lukin O, Demoiseaux R, Buzko A, Shivanyuk A. Drug- and lead-likeness, target class, and molecular diversity analysis of 7.9 million commercially available organic compounds provided by 29 suppliers. J Chem Inf Model. 2010 Apr 26;50(4):470-9. PubMed, CrossRef
  12. Thomas AH. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comp. Chem. 1996;17:490-519.
  13. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The protein databank. Nucleic Acids Res. 2000;28:235-242.
  14. Balinskyi OM, Sudakov OO, Platonov MO. Small-molecule ligand search for protein interaction domains involving shape-based molecular modeling methods. Bulletin of Taras Shevchenko National University of Kyiv. Series Physics & Mathematics. 2012;3:287-291.
  15. Benini S, Gessa C, Ciurli S. Bacillus pasteurii urease: a heteropolymeric enzyme with a binuclear nickel active site. Soil Biol. Biochem. 1996;28:819-821.
  16. McMartin C, Bohacek RS. QXP: powerful, rapid computer algorithms for structure-based drug design. J Comput Aided Mol Des. 1997 Jul;11(4):333-44. PubMed
  17. Corbeil CR, Williams CI, Labute P. Variability in docking success rates due to dataset preparation. J Comput Aided Mol Des. 2012 Jun;26(6):775-86. PubMed, PubMedCentral, CrossRef
  18. Chang DT, Oyang YJ, Lin JH. MEDock: a web server for efficient prediction of ligand binding sites based on a novel optimization algorithm. Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W233-8. PubMed, PubMedCentral
  19. Warren GL, Andrews CW, Capelli AM, Clarke B, LaLonde J, Lambert MH, Lindvall M, Nevins N, Semus SF, Senger S, Tedesco G, Wall ID, Woolven JM, Peishoff CE, Head MS. A critical assessment of docking programs and scoring functions. J Med Chem. 2006 Oct 5;49(20):5912-31. PubMed
  20. Sudakov OO, Balinskyi OM, Platonov MO, Kovalskyy DB. Geometric filters for protein–ligand complexes based on phenomenological molecular models. Biopolym Cell. 2013;29:395-400.
  21. Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model. 2005 Jan-Feb;45(1):160-9. PubMed
  22. Irwin JJ, Shoichet BK. ZINC–a free database of commercially available compounds for virtual screening. J Chem Inf Model. 2005 Jan-Feb;45(1):177-82. PubMed, PubMedCentral
  23. Braga RC, Andrade CH. Assessing the performance of 3D pharmacophore models in virtual screening: how good are they? Curr Top Med Chem. 2013;13(9):1127-38. Review. PubMed
  24. Verdonk ML, Berdini V, Hartshorn MJ, Murray CW, Taylor RD, Watson J. Virtual screening using protein-ligand docking: avoiding artificial enrichment. J. Chem. Inf. Model. 2004:44:793-806.
  25. Kirchmair J, Markt P, Distinto S, Wolber G, Langer TJ. Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection-What can we learn from earlier mistakes? Comput Aid Mol. Design. 2008;22:213-228.
  26. Sonego P, Kocsor A, Pongor S. ROC analysis: applications to the classification of biological sequences and 3D structures. Brief Bioinform. 2008 May;9(3):198-209. Review. PubMed, CrossRef
  27. Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Müller M. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011 Mar 17;12:77. PubMed, PubMedCentral, CrossRef
  28. Truchon JF, Bayly CI. Evaluating virtual screening methods: good and bad metrics for the “early recognition” problem. J Chem Inf Model. 2007 Mar-Apr;47(2):488-508. Epub 2007 Feb 9. PubMed
  29. Thangapandian S, John S, Sakkiah S, Lee KW. Ligand and structure based pharmacophore modeling to facilitate novel histone deacetylase 8 inhibitor design. Eur J Med Chem. 2010 Oct;45(10):4409-17. PubMed, CrossRef
  30. Héléna AG, Gilles M, Dragos H, Alban A, Sylvain L, Philippe V, Alexandre V. Generative Topographic Mapping-Based Classification Models and Their Applicability Domain: Application to the Biopharmaceutics Drug Disposition Classification System (BDDCS). J. Chem. Inf. Model. 2013;53:3318-3325.
  31. Kireeva N., Baskin I. I., Gaspar H. A., Horvath D., Marcou G., Varnek A. Generative Topographic Mapping (GTM): Universal Tool for Data Visualization, Structure-Activity Modeling and Dataset Comparison. Mol. Inf. 2012;31:301-312.
  32. Abdul W., Shandana A., Muhammad R., Syed B. J., Taj Ur R., Sahib G., Mukhtiar H. Pakhtunkhwa Molecular Docking Study of 5-substituted-8-methyl-2H-pyrido [1, 2-a] pyrimidine-2, 4 (3H) – diones As Inhibitors of Basilluspasteurii urease. J. Life Sci. 2013;1:145-153.
  33. Hurmach VV, Balinskyi OM, Platonov MO, Boyko OM, Borysko PO, Prylutskyy YI. Design of potentially active ligands for SH2 domains by molecular modeling methods. Biopolym Cell. 2014;30:321-325.
  34. Needleman SB, Wunsch CD. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443-53. PubMed
  35. Chakraborty A, Bandyopadhyay S. FOGSAA: Fast Optimal Global Sequence Alignment Algorithm. Sci Rep. 2013;3:1746. PubMed, PubMedCentral, CrossRef
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