Docking studies on hERG model


Anna Maria Capelli1, Aldo Feriani2, Frank E Blaney3, Diego Dal Ben1, Giovanna Tedesco1, and Alfonso Pozzan4. (1) Computational, Analytical and Structural Sciences, GlaxoSmithKline, Medicines Research Centre Via Alessandro, Fleming 4 37135, Verona, Italy, (2) GlaxoSmithKline Research Centre, (3) Computational, Analytical & Structural Studies, GlaxoSmithKline, Harlow, Essex, England, (4) Chemistry Department, Computational Chemistry and Compound Diversity Unit, Verona Research Centre, Glaxo Smith Kline S.p.A, Via Fleming 4, 37100 Verona, Italy
Drug-induced QT interval prolongation, which is a major risk for torsades de pointes arrhytmia, can be related to the inhibition of the K+ channel encoding by human ether a go-go related gene (HERG). As a consequence, evaluation of potential pharmacological liability associated to hERG is an important aspect of the drug discovery process. In this study, docking experiments in an in house hERG receptor model were performed to study a set of hERG standards. Validation of the poses obtained was then performed using site-directed mutagenesis experiments reported in the literature and the affinity of the ligands correlated with empirical scoring functions. The method was then used to perform docking experiments of in house ligands and used to drive drug design activities.

8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix

Division of Chemical Information

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004