TY  - JOUR
A1  - Werner, Tim
A1  - Geppert, Tim
A1  - Tanrikulu, Yusuf
A1  - Proschak, Ewgenij
A1  - Schneider, Gisbert
T1  - Pseudoreceptor-based pocket selection in a molecular dynamics simulation of the histamine H4 receptor
T2  - Chemistry central journal
N2  - There is a renewed interest in pseudoreceptor models which enable computational chemists to bridge the gap of ligand- and receptor-based drug design. We developed a pseudoreceptor model for the histamine H4 receptor (H4R) based on five potent antagonists representing different chemotypes. Here we present the selection of potential ligand binding pockets that occur during molecular dynamics (MD) simulations of a homology-based receptor model. We present a method for prioritizing receptor models according to their match with the consensus ligand-binding mode represented by the pseudoreceptor. In this way, ligand information can be transferred to receptor-based modelling. We use Geometric Hashing to match three-dimensional points in Cartesion space. This allows for the rapid translation- and rotation-free comparison of atom coordinates, which also permits partial matching. The only prerequisite is a hash table, which uses distance triplets as hash keys. Each time a distance triplet occurring in the candidate point set which corresponds to an existing key, the match is represented by a vote of the respective key. Finally, the global match of both point sets can be easily extracted by selection of voted distance triplets. The results revealed a preferred ligand-binding pocket in H4R, which would not have been identified using an unrefined homology model of the protein. The key idea was to rely on ligand information by pseudoreceptor modelling.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6787
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-66707
SN  - 1752-153X
N1  - © 2009 Werner et al; licensee BioMed Central Ltd.
VL  - 3
IS  - P74
SP  - 1
EP  - 1
PB  - BioMed Central
CY  - London
ER  -