10.5281/zenodo.45774
https://zenodo.org/records/45774
oai:zenodo.org:45774
Jansen, Chimed
Chimed
Jansen
Vrije Universiteit Amsterdam
Kooistra, Albert J.
Albert J.
Kooistra
Vrije Universiteit Amsterdam
Kanev, Georgi K.
Georgi K.
Kanev
Vrije Universiteit Amsterdam
Leurs, Rob
Rob
Leurs
Vrije Universiteit Amsterdam
de Esch, Iwan J.P.
Iwan J.P.
de Esch
Vrije Universiteit Amsterdam
de Graaf, Chris
Chris
de Graaf
Vrije Universiteit Amsterdam
PDEStrIAn: A phosphodiesterase structure and ligand interaction annotated database as a tool for structure-based drug design
Zenodo
2016
phosphodiesterases
crystal structures
drug design
structure-based drug design
PDEs
2016-02-08
http://pdestrian.vu-compmedchem.nl
http://www.pde4npd.eu
10.1021/acs.jmedchem.5b01813
26908025
https://zenodo.org/communities/eu
Creative Commons Zero v1.0 Universal
A systematic analysis is presented of the 220 phosphodiesterase (PDE) catalytic domain crystal structures present in the Protein Data Bank (PDB) with a focus on PDE-ligand interactions. The consistent structural alignment of 57 PDE ligand binding site residues enables the systematic analysis of PDE-ligand Interaction FingerPrints (IFPs), the identification of subtype-specific PDE-ligand interaction features, and the classification of ligands according to their binding modes. We illustrate how systematic mining of this phosphodiesterase structure and ligand interaction annotated (PDEStrIAn) database provides new insights into how conserved and selective PDE interaction hot spots can accommodate the large diversity of chemical scaffolds in PDE ligands. A substructure analysis of the co-crystalized PDE ligands in combination with those in the ChEMBL database provides a toolbox for scaffold hopping and ligand design. These analyses lead to an improved understanding of the structural requirements of PDE binding that will be useful in future drug discovery studies.
The newest version of PDEStrIAn is available at http://pdestrian.vu-compmedchem.nl
European Commission
10.13039/501100000780
602666
Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases