GPCRdb in 2018: adding GPCR structure models and ligands

TY - JOUR

T1 - GPCRdb in 2018

T2 - adding GPCR structure models and ligands

AU - Pándy-Szekeres, Gáspár

AU - Munk, Christian

AU - Tsonkov, Tsonko M

AU - Mordalski, Stefan

AU - Harpsøe, Kasper

AU - Hauser, Alexander S

AU - Bojarski, Andrzej J

AU - Gloriam, David E

N1 - © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects. Herein, we report GPCRome-wide homology models of unprecedented quality, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability. Based on the strategy of 'Less model - more Xtal', each model exploits both a main template and alternative local templates. This achieved higher similarity to new structures than any of the existing resources, and refined crystal structures with missing or distorted regions. Models are provided for inactive, intermediate and active states-except for classes C and F that so far only have inactive templates. The ligand database has separate browsers for: (i) target selection by receptor, family or class, (ii) ligand filtering based on cross-experiment activities (min, max and mean) or chemical properties, (iii) ligand source data and (iv) commercial availability. SMILES structures and activity spreadsheets can be downloaded for further processing. Furthermore, three recent landmark publications on GPCR drugs, G protein selectivity and genetic variants have been accompanied with resources that now let readers view and analyse the findings themselves in GPCRdb. Altogether, this update will enable scientific investigation for the wider GPCR community. GPCRdb is available at http://www.gpcrdb.org.

AB - G protein-coupled receptors are the most abundant mediators of both human signalling processes and therapeutic effects. Herein, we report GPCRome-wide homology models of unprecedented quality, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability. Based on the strategy of 'Less model - more Xtal', each model exploits both a main template and alternative local templates. This achieved higher similarity to new structures than any of the existing resources, and refined crystal structures with missing or distorted regions. Models are provided for inactive, intermediate and active states-except for classes C and F that so far only have inactive templates. The ligand database has separate browsers for: (i) target selection by receptor, family or class, (ii) ligand filtering based on cross-experiment activities (min, max and mean) or chemical properties, (iii) ligand source data and (iv) commercial availability. SMILES structures and activity spreadsheets can be downloaded for further processing. Furthermore, three recent landmark publications on GPCR drugs, G protein selectivity and genetic variants have been accompanied with resources that now let readers view and analyse the findings themselves in GPCRdb. Altogether, this update will enable scientific investigation for the wider GPCR community. GPCRdb is available at http://www.gpcrdb.org.

KW - Journal Article

U2 - 10.1093/nar/gkx1109

DO - 10.1093/nar/gkx1109

M3 - Journal article

C2 - 29155946

SN - 0305-1048

VL - 46

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - D1

M1 - gkx1109

ER -