In silico ligand-based (LB) and docking-based (DB) 3D-QSAR study of potent Chk2 inhibitors

F. A. Pasha, M. Muddassar, So Ha Lee, Taebo Sim, Jung Mi Hah, Seung Joo Cho

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Isothiazole carboxamidine compounds are potent ATP competitive Chk2 inhibitors. A series of compounds with Chk2 inhibitory activity were taken from literature and different 3D-QSAR models have been generated with Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). In first scheme LB-QSAR models were generated using fully optimized geometries by PM3 approach giving reasonable statistics of CoMFA (q2=0.88, r2=0.96 and rpredictive 2=0.60) and COMSIA(q2=0.918 r2=0.99 and r prediaive2=0.55). In second and third scheme the ligands 7 docked in to receptor protein (PDB 2CN8). Consequently, two most plausible modes were identified and used as initial templates. The docked conformer based CoMFA model shows good correlation with activity (q2=0.91, r 2=0.99 and rpredictive2 =0.84). Whereas in CoMSIA, the steric and hydrophobic and donor field jointly give a better statistics (q2=0.92 r2=0.99 and r predictive2 =0.53). These findings might be helpful to design more potent Chk2 inhibitors.

Original languageEnglish
Title of host publicationProceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007
Pages38-42
Number of pages5
DOIs
Publication statusPublished - 2007
EventFrontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007 - Jeju Island, Korea, Republic of
Duration: 2007 Oct 112007 Oct 13

Publication series

NameProceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007

Other

OtherFrontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007
CountryKorea, Republic of
CityJeju Island
Period07/10/1107/10/13

Keywords

  • 3D-QSAR
  • Chk2
  • CoMFA
  • CoMSIA
  • Docking

ASJC Scopus subject areas

  • Computer Science Applications
  • Information Systems

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    Pasha, F. A., Muddassar, M., Lee, S. H., Sim, T., Hah, J. M., & Cho, S. J. (2007). In silico ligand-based (LB) and docking-based (DB) 3D-QSAR study of potent Chk2 inhibitors. In Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007 (pp. 38-42). [4524076] (Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007). https://doi.org/10.1109/FBIT.2007.86