Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811
USA

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Integrated Ligand Based Pharmacophore Model Derived from Diverse FAAH Covalent Ligand Classes

Author(s): Lingling Shen, Hongwei Huang, Alexandros Makriyannis, Luke S. Fisher.

Abstract:

3D pharmacophore modeling is an important computational methodology for ligand-enzyme binding interactions in drug discovery. More specifically, a consensus pharmacophore model derived from diverse ligands is a key determinant upon which the prediction power of computational models is based for designing novel ligands. In this work, by merging the important pharmacophore features based on four classes of covalent FAAH ligands, and then integrating the exclusion volume spheres derived from the crystal structure, we created for the first time an integrated FAAH pharmacophore model to describe the ligand-enzyme binding interactions. This new integrated FAAH pharmacophore model can correctly predict the covalent ligand binding mode, which correlates with the SAR data. The study is expected to provide insights into novel covalent ligand-FAAH binding interactions, and facilitate the design of covalent ligands against FAAH.

Keywords: Covalent, fatty acid amide hydrolase (FAAH), pharmacophore, docking

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2012
Page: [330 - 334]
Pages: 5
DOI: 10.2174/157340912803519615
Price: $58