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http://dx.doi.org/10.5012/bkcs.2006.27.2.266

Quantitative Structure-Activity Relationships and Molecular Docking Studies of P56 LCK Inhibitors  

Bharatham, Nagakumar (Division of Applied Life Science, Environmental Biotechnology National Core Research Center, Gyongsang National University)
Bharatham, Kavitha (Division of Applied Life Science, Environmental Biotechnology National Core Research Center, Gyeongsang National University)
Lee, Keun-Woo (Division of Applied Life Science, Environmental Biotechnology National Core Research Center, Gyeongsang National University)
Publication Information
Bulletin of the Korean Chemical Society / v.27, no.2, 2006 , pp. 266-272 More about this Journal
Abstract
Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.
Keywords
P56 LCK; Protein tyrosine kinase (PTKs); Benzothiazole derivatives; 3D-QSAR; GOLD molecular docking;
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