A new paradigm for pattern recognition of drugs | Journal of Computer-Aided Molecular Design Skip to main content
Springer Nature Link
Log in

A new paradigm for pattern recognition of drugs

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Abstract

A new paradigm is suggested for pattern recognition of drugs. The approach is based on the combined application of the 4D/3D quantitative structure–activity relationship (QSAR) algorithms BiS and ConGO. The first algorithm, BiS/MC (multiconformational), is used for the search for the conformers interacting with a receptor. The second algorithm, ConGO, has been suggested for the detailed study of the selected conformers' electron density and for the search for the electron structure fragments that determine the pharmacophore and antipharmacophore parts of the compounds. In this work we suggest using a new AlteQ method for the evaluation of the molecular electron density. AlteQ describes the experimental electron density (determined by low-temperature highly accurate X-ray analysis) much better than a number of quantum approaches. Herein this is shown using a comparison of the computed electron density with the results of highly accurate X-ray analysis. In the present study the desirability function is used for the first time for the analysis of the effects of the electron structure in the process of pattern recognition of active and inactive compounds. The suggested method for pattern recognition has been used for the investigation of various sets of compounds such as DNA-antimetabolites, fXa inhibitors, 5-HT1A, and α1-AR receptors inhibitors. The pharmacophore and antipharmacophore fragments have been found in the electron structures of the compounds. It has been shown that the pattern recognition cross-validation quality for the datasets is unity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
¥17,985 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Japan)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16

Similar content being viewed by others

Notes

  1. www.modelchem.ru

References

  1. Khalil M, Weaver DF (1990) J Pharm Pharmacol 42:349

    CAS  Google Scholar 

  2. Weaver DF, Knight JL (1998) Seizure 7:347

    Article  Google Scholar 

  3. Khlebnikov AI (1997) Pharm Chem J 31:147

    Article  Google Scholar 

  4. Kasabov N (2007) Pattern Recognit Lett 28:673

    Article  Google Scholar 

  5. Bartzatt R (2005) Eur J Pharm Biopharm 59:63

    Article  CAS  Google Scholar 

  6. Keith Davies E, Glick M, Harrison KN, Graham Richards W (2002) Inc J Comput Chem 23:1544

    Article  CAS  Google Scholar 

  7. Kowalski BR, Bender CF (1975) Naturwissenschaften 62:10

    Article  CAS  Google Scholar 

  8. Bartzatt R, Donigan L (2006) AAPS PharmSciTech 7:E35

    Article  Google Scholar 

  9. Tetko IV, Aksenova TI, Patiokha AA, Villa AEP, Welsh WJ, Zielinski WL, Livingstone DJ (1999) Anal Chem 71:2431

    Article  CAS  Google Scholar 

  10. Potashnikov PF, Fetisov VI, Ezhov VV, Dan'shin BI, Sokol'skii GA (1980) Pharm Chem J 14:61

    CAS  Google Scholar 

  11. Potemkin VA, Bartashevich EV, Grishina MA, Guccione S (2001) In: Holtje H-D, Sippl W (eds) Rational approaches to drug design. Proceedings of the 13th European symposium on quantitative structure-activity relationships, QSAR 2000. Prous Science Publishers, Barcelona, Spain, pp 349–353

  12. Potemkin VA, Grishina MA, Bartashevich EV (2007) J Struct Chem 48:155

    Article  CAS  Google Scholar 

  13. Potemkin VA, Arslambekov RM, Bartashevich EV, Grishina MA, Belik AV, Perspicace S, Guccione S (2002) J Struct Chem 43:1045

    Article  CAS  Google Scholar 

  14. http://www.modelchem.ru

  15. Grishina MA, Potemkin VA (2007) Drugs Future 32(Suppl A):112

  16. Pereyaslavskaya ES, Potemkin VA, Grishina MA, Bartashevich EV (2007) Drugs Future 32(A):87

    Google Scholar 

  17. Potemkin VA, Grishina MA, Fedorova OV, Rusinov GL, Ovchinnikova IG, Ishmetova RI (2003) Pharm Chem J 37:468

    Article  CAS  Google Scholar 

  18. Grishina MA, Pogrebnoi AA, Potemkin VA, Zrakova TYu (2005) Pharm Chem J 39:509

    Article  CAS  Google Scholar 

  19. Potemkin VA, Grishina MA, Belik AV, Chupakhin ON (2002) Pharm Chem J 36:22

    Article  CAS  Google Scholar 

  20. Grishina MA, Potemkin VA, Rusinov GL, Bartashevich EV, Guccione S, Perspicace S, Chupakhin ON (2002) In: From genes to drugs via crystallography, 33rd crystallographic course at the E. Majorana Centre, Erice, Italy, 23 May–2 June

  21. Mikuchina K, Potemkin V, Grishina M, Laufer S (2002) Arch Pharm Pharm Med Chem 335:C74

    Google Scholar 

  22. Grishina MA, Potemkin VA (2003) In: IXth International seminar on inclusion compounds (ISIC-9), Novosibirsk, Russia, 23–27 June

  23. Grishina MA, Pogrebnoi AA, Potemkin VA, Zrakova TYu (2005) Pharm Chem J 39:509

    Article  CAS  Google Scholar 

  24. Grishina MA, Mikushina KM, Potemkin VA (2006) In: The 16th European symposium on quantitative structure-activity relationships and molecular modelling, Mediterranean Sea, Italy, 10–17 September

  25. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) Nucleic Acids Res 28:235

    Article  CAS  Google Scholar 

  26. Gao Y-G, Wang AH-J (1991) Anticancer Drug Des 6:137

    CAS  Google Scholar 

  27. Wang Z, Canagarajah BJ, Boehm JC, Kassisi S, Corb MH, Young PR, Abdel- Meguid S, Adams JL, Goldsmith EJ (1998) Structure 6:1117

    Article  CAS  Google Scholar 

  28. Bartashevich EV, Potemkin VA, Grishina MA, Belik AV (2002) J Struct Chem 43:1033

    Article  CAS  Google Scholar 

  29. Potemkin VA, Bartashevich EV, Belik AV (1996) Russ J Phys Chem A 70:411

    Google Scholar 

  30. Harrington EC (1965) Ind Qual Control 21:494

    Google Scholar 

  31. Hsieh K-L, Tong L-I, Chiu H-P, Yeh H-Y (2005) Comput Ind Eng 49:556

    Article  Google Scholar 

  32. Doweyko AM (1988) J Med Chem 31:1396

    Article  CAS  Google Scholar 

  33. Doweyko AM (1991) J Math Chem 7:273

    Article  CAS  Google Scholar 

  34. Doweyko AM (1994) J Med Chem 37:1769

    Article  CAS  Google Scholar 

  35. Kaminski JJ, Doweyko AM (1997) J Med Chem 40:427

    Article  CAS  Google Scholar 

  36. Tsirelson VG, Stash AI, Potemkin VA, Rykounov AA, Shutalev AD, Zhurova EA, Zhurov VV, Pinkerton AA, Gurskaya GV, Zavodnik VE (2006) Acta Crystallogr B 62:676

    Article  CAS  Google Scholar 

  37. Tsirelson V, Stash A, Zhurova E, Zhurov V, Pinkerton AA, Zavodnik V, Shutalev A, Gurskaya G, Rykounov A, Potemkin V (2005) Acta Crystallogr A 61:C427

    Article  Google Scholar 

  38. Clark T (1985) Handbook of computational chemistry; a practical guide to chemical structure and energy calculations. Wiley-Interscience, 352 pp

  39. Grant JA, Pickup BT (1995) J Phys Chem 99:3503

    Article  CAS  Google Scholar 

  40. Vaz RJ (1997) Quant Struct Act Relat 16:303

    Article  CAS  Google Scholar 

  41. Weinstein et al (1992) Science 258:447

    Article  CAS  Google Scholar 

  42. van Osdol et al (1994) J Natl Cancer Inst 86:1853

    Article  Google Scholar 

  43. Herron D, Goodson Th, Wiley MR, Weir LC, Kyle JA, Yee YK, Tebbe AL, Tinsley JM, Mendel D, Masters JJ, Franciskovich JB, Sawyer JS, Beight DW, Ratz AM, Milot G, Hall SE, Klimkowski VJ, Wikel JH, Eastwood BJ, Towner RD, Gifford-Moore DS, Craft TJ, Smith JF (2000) J Med Chem 43:859

    Article  CAS  Google Scholar 

  44. Yee YK, Tebbe AL, Linebarger JH, Beight DW, Craft TJ, Gifford-Moore DS, Goodson Th, Herron D, Klimkowski VJ, Kyle JA, Sawyer JS, Smith JF, Tinsley JM, Towner RD, Weir LC, Wiley MR (2000) J Med Chem 43:873

    Article  CAS  Google Scholar 

  45. Guccione S, Doweyko AM, Chen H, Barretta GU, Balzano F (2000) J Comput Aided Mol Des 14:647

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The work is supported by RFBR (grants 07-03-96041, 07-04-96053) and Human Capital Foundation. Besides, we are thankful to Tsirelson V.G. and Stash A.I. for the low-temperature highly accurate X-ray results for a number of molecules.

Author information

Authors and Affiliations

  1. Chemical Department, Chelyabinsk State University, Br. Kashirianich, 129, Chelyabinsk, 454021, Russian Federation

    Vladimir A. Potemkin & Maria A. Grishina

Authors
  1. Vladimir A. Potemkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria A. Grishina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria A. Grishina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Potemkin, V.A., Grishina, M.A. A new paradigm for pattern recognition of drugs. J Comput Aided Mol Des 22, 489–505 (2008). https://doi.org/10.1007/s10822-008-9203-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10822-008-9203-x

Keywords

Search

Navigation