Binding Mode Prediction of PDE4 Inhibitors: A Comparison of Modelling Methods

作者：Neale Diana S; Thompson Philip E; White Paul J; Chalmers David K; Yuriev Elizabeth; M****lack David T^*

来源：Australian Journal of Chemistry, 2010, 63(3): 396-404.

DOI：10.1071/CH09463

Molecular modelling is widely used in support of medicinal chemistry programs, with several theoretical approaches used in attempts to expedite drug discovery. In this study, three methods - molecular docking (Glide), shape similarity (ROCS), and pharmacophore modelling (Phase) - were evaluated for their ability to reproduce experimentally determined binding modes of 25 PDE4 inhibitors, identified by X-ray crystallography. Molecular docking was able to provide a good approximation (RMSD less than 2 angstrom) in 59% of cases, when considering the top binding pose. The pairwise comparisons, using molecular shape similarity, gave good matches in 42% of cases. Pharmacophore models were unable to predict good binding modes for a series of PDE4 inhibitors.

• 出版日期2010