Modeling HERG and its interactions with drugs: recent advances in light of current potassium channel simulations.
The hERG K(+) channel is responsible for the rapid delayed rectifier current in cardiac myocytes, and a block of its functioning may be related with the (inherited or drug-induced) long QT syndrome. For this reason, in recent times, some interest has arisen around computational studies aimed at developing hERG/drug models for the prediction of drug binding (docking) modes, in view of the assessment of the hERG blocking potential. On the other hand, voltage-gated K(+) channels have been the subject of molecular simulations for several years, and rigorous protocols for studying the main aspects of their functions (permeation, gating, voltage sensing) have been published. In this article, we briefly introduce these classical computational works on K(+) channels, and then review in depth the reports on the latest advanced modeling studies on hERG. The aim is to put the hERG modeling work in the more general context of the ion channel simulations field, to show the peculiarity of hERG on the one side, and also to indicate some possible new avenues in the use of modeling techniques to increase our knowledge of this important channel.
Recanatini
Maurizio
M
University of Bologna, Department of Pharmaceutical Sciences, Via Belmeloro 6, 40126 Bologna, Italy. maurizio.recanatini@unibo.it
Cavalli
Andrea
A
Masetti
Matteo
M
D000595:Amino Acid Sequence; D003198:Computer Simulation; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism; D011487:Protein Conformation
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D008024:Ligands; D011188:Potassium