통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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Hologram Based QSAR Analysis of Caspase-3 Inhibitors

  • Sathya., B (Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology)
  • 투고 : 2018.04.17
  • 심사 : 2018.06.25
  • 발행 : 2018.06.30
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초록

Caspases, a family of cysteinyl aspartate-specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage because the activation of caspases-3 stimulates a signalling pathway that ultimately leads to the death of the cell. In this study, Hologram based Quantitative Structure Activity Relationship (HQSAR) models was generated on a series of Caspase-3 inhibitors named 3, 4-dihydropyrimidoindolones derivatives. The best HQSAR model was obtained using atoms, bonds, and hydrogen atoms (A/B/H) as fragment distinction parameter using hologram length 61 and 3 components with fragment size of minimum 5 and maximum 8. Significant cross-validated correlation coefficient ($q^2=0.684$) and non cross-validated correlation coefficients ($r^2=0.754$) were obtained. The model was then used to evaluate the eight external test compounds and its $r^2_{pred}$ was found to be 0.559. Contribution map show that presence of pyrrolidine sulfonamide ring and its bulkier substituent's makes big contributions for improving the biological activities of the compounds.

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