Structural Basis of Amino Pyrimidine Derivatives for Inhibitory Activity of PKC-θ: 3D-QSAR and Molecular Docking Studies

Om Silakari; Sukhvir Chand; Malkeet Singh Bahia

doi:10.1002/minf.201100123

Structural Basis of Amino Pyrimidine Derivatives for Inhibitory Activity of PKC-θ: 3D-QSAR and Molecular Docking Studies

Mol Inform. 2012 Sep;31(9):659-68. doi: 10.1002/minf.201100123. Epub 2012 Aug 23.

Authors

Om Silakari¹, Sukhvir Chand², Malkeet Singh Bahia²

Affiliations

¹ Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India tel: +919501542696, fax: +911752283075. omsilakari@rediffmail.com.
² Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India tel: +919501542696, fax: +911752283075.

PMID: 27477816
DOI: 10.1002/minf.201100123

Abstract

In the present study, 3D-QSAR analysis was performed on a set of 56 amino pyrimidine PKC-θ inhibitors utilizing docking based alignment. The best 3D-QSAR model exhibited the highest value of Q(2) (0.825) and also displayed high values of R(2) (0.937), F (184.600) and low SD (0.240). The selected model was validated by determining the Pearson-r (0.915) for test set molecules. Docking simulation was carried out to explore the binding interactions of the molecules with active site amino acid residues of the receptor and subsequently to validate the generated 3D-QSAR model. The results of 3D-QSAR and docking analysis exerted complementary fit that strengthen the stability and reliability of the generated model. Therefore, the combined study of 3D-QSAR and docking analysis may successfully be used for the rational designing of new potent congeners.

Keywords: 3D-QSAR; Amino pyridine inhibitors; Docking; Inflammation, PKC-θ.