Abstract
Many proteins, such as the hERG K+ channel or the HIV-1 protease, have a high degree of rotational symmetry. If the binding site of a ligand is composed of symmetrical subunits, the analysis of the docking poses of ligands is quite challenging. In the case of hERG, the four-fold symmetry of the entire channel is fully reflected in the binding site, which allows up to four poses with different coordinates of the ligand, but an identical interaction pattern. In light of our docking studies into the hERG potassium channel, we developed an algorithm (ROTALI) to detect the poses that are duplicates due to the symmetry of the channel. This led to a reduction in the number of poses to be considered in the subsequent steps by up to 52%.
Highlights
The hERG potassium channel plays an important role in the third phase of heart repolarization, where the most important current is the rapid inward rectifier current (Ikr)
Ikr is created by a flow of potassium ions through the cell membrane, caused by the opening of the hERG channel [1]
The long QT syndrome (LQTS) is correlated with a cardiac arrhythmia called Torsade de Pointes (TdP), which could potentially be lethal
Summary
The hERG potassium channel plays an important role in the third phase of heart repolarization, where the most important current is the rapid inward rectifier current (Ikr). Propafenone derivatives docked into the hERG channel When a docking operation is performed in a symmetric binding site, it is possible to obtain the same pose in four different directions.
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