Computational Approaches to Predict hERG K Channel Block

Computational Approaches to Predict hERG K+ Channel Block 

The evolving structural insights into the hERG drug-binding site show that this channel has a relatively larger inner cavity, with many aromatic and polar residues intricately positioned to interact with drugs. Utilization of in silico techniques, refined 

The potential of drugs to cause QT prolongation and the associated risk of cardio-toxicity remains an important issue in drug development. Although the advent of automated electrophysiological systems and other predinical screens has helped in early identification of hERG channel blockers, the outcome can be highly unsatisfactory. The process is wasteful and expensive and the development of potentially valuable compounds is halted. The wealth of information continually uncovered 

We would like to thank all recent members of the Mitcheson lab for their help and support. In particular, we are grateful to Dr Phill Stansfeld for his modeling expertise and assistance with the figures, and to Professor Mike Sutcliffe (University of Manchester) who supervised the modeling work and has been a pleasure to work with. We are also grateful to Dr Cavalli and Professor Recanatini for providing the coordinates of their pharmacophore model. 

1 Hille, B. (2001) Ion Channels of Excitable Membranes, 3rdedn, Sinauer Associates, Sunderland, MA. 

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