Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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P56 LCK Inhibitor Identification by Pharmacophore Modelling and Molecular Docking

  • Bharatham, Nagakumar (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Gyeongsang National University) ;
  • Bharatham, Kavitha (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Gyeongsang National University) ;
  • Lee, Keun-Woo (Department of Biochemistry, Division of Applied Life Science, Environmental Biotechnology National Core Research Center (EB-NCRC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Gyeongsang National University)
  • Published : 2007.02.20
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Abstract

Pharmacophore models for lymphocyte-specific protein tyrosine kinase (P56 LCK) were developed using CATALYST HypoGen with a training set comprising of 25 different P56 LCK inhibitors. The best quantitative pharmacophore hypothesis comprises of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic aliphatic and one ring aromatic features with correlation coefficient of 0.941, root mean square deviation (RMSD) of 0.933 and cost difference (null cost-total cost) of 66.23. The pharmacophore model was validated by two methods and the validated model was further used to search databases for new compounds with good estimated LCK inhibitory activity. These compounds were evaluated for their binding properties at the active site by molecular docking studies using GOLD software. The compounds with good estimated activity and docking scores were evaluated for physiological properties based on Lipinski's rules. Finally 68 compounds satisfied all the properties required to be a successful inhibitor candidate.

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