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

doi:10.1109/FBIT.2007.86

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

KU-KIST Graduate School of Converging Science and Technology

Research output: Chapter in Book/Report/Conference proceeding › Conference 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 r_predictive 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 r_predictive² =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 language	English
Title of host publication	Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007
Pages	38-42
Number of pages	5
DOIs	https://doi.org/10.1109/FBIT.2007.86
Publication status	Published - 2007
Event	Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007 - Jeju Island, Korea, Republic of Duration: 2007 Oct 11 → 2007 Oct 13

Publication series

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

Other

Other	Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007
Country/Territory	Korea, Republic of
City	Jeju Island
Period	07/10/11 → 07/10/13

Keywords

3D-QSAR
Chk2
CoMFA
CoMSIA
Docking

ASJC Scopus subject areas

Computer Science Applications
Information Systems

Access to Document

10.1109/FBIT.2007.86

Cite this

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). Article 4524076 (Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007). https://doi.org/10.1109/FBIT.2007.86

In silico ligand-based (LB) and docking-based (DB) 3D-QSAR study of potent Chk2 inhibitors. / Pasha, F. A.; Muddassar, M.; Lee, So Ha et al.
Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007. 2007. p. 38-42 4524076 (Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution

Pasha, FA, Muddassar, M, Lee, SH, Sim, T, Hah, JM & Cho, SJ 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., 4524076, Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007, pp. 38-42, Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007, Jeju Island, Korea, Republic of, 07/10/11. https://doi.org/10.1109/FBIT.2007.86

Pasha FA, Muddassar M, Lee SH, Sim T, Hah JM, Cho SJ. 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. 2007. p. 38-42. 4524076. (Proceedings of the Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007). doi: 10.1109/FBIT.2007.86

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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.",

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AU - Hah, Jung Mi

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AB - 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.

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

Abstract

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Keywords

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