How to solve the problems of docking into a symmetric binding site: The example of the hERG channel

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%.