How to solve the problems of docking into a symmetric binding site

Author(s)
Andrea Schiesaro, Lars Richter, Gerhard F Ecker
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%.

Organisation(s)
Journal
Scientia Pharmaceutica
Volume
81
Pages
677-82
No. of pages
6
ISSN
0036-8709
DOI
https://doi.org/10.3797/scipharm.1307-01
Publication date
2013
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry, 102009 Computer simulation
Sustainable Development Goals
SDG 3 - Good Health and Well-being
Portal url
https://ucrisportal.univie.ac.at/en/publications/81d79ae4-fe06-4d03-8a35-630d70f7d4d1