Dataset Information

The GPCR Network: a large-scale collaboration to determine human GPCR structure and function.

ABSTRACT: G protein-coupled receptors (GPCRs) are targeted by ?30-40% of marketed drugs, and their key roles in normal physiology and in disease demonstrate that an understanding of their structure and function is valuable to researchers in both basic science and drug discovery. However, until recently, detailed structural information on this protein family was limited by challenges in X-ray crystallographic analysis of such membrane proteins. The GPCR Network was created in 2010 with the goal of structurally characterizing 15-25 representative human GPCRs within 5 years, based on an active outreach programme addressing an interdisciplinary community of scientists interested in GPCR structure, chemistry and biology. Here, we provide an overview of how this collaborative effort has enabled the structural determination and characterization of eight human GPCRs so far, and discuss some of the challenges that remain in gaining more detailed insights into structure-function relationships in this receptor superfamily.

SUBMITTER: Stevens RC

PROVIDER: S-EPMC3723354 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The GPCR Network: a large-scale collaboration to determine human GPCR structure and function.

Stevens Raymond C RC Cherezov Vadim V Katritch Vsevolod V Abagyan Ruben R Kuhn Peter P Rosen Hugh H Wüthrich Kurt K

Nature reviews. Drug discovery 20121214 1

G protein-coupled receptors (GPCRs) are targeted by ∼30-40% of marketed drugs, and their key roles in normal physiology and in disease demonstrate that an understanding of their structure and function is valuable to researchers in both basic science and drug discovery. However, until recently, detailed structural information on this protein family was limited by challenges in X-ray crystallographic analysis of such membrane proteins. The GPCR Network was created in 2010 with the goal of structur ...[more]

PMID: 23237917

Similar Datasets

Project description:Conventional generators in power grids are steadily substituted with new renewable sources of electric power. The latter are connected to the grid via inverters and as such have little, if any rotational inertia. The resulting reduction of total inertia raises important issues of power grid stability, especially over short-time scales. With the motivation in mind to investigate how inertia reduction influences the transient dynamics following a fault in a large-scale electric power grid, we have constructed a model of the high voltage synchronous grid of continental Europe. To assess grid stability and resilience against disturbance, we numerically investigate frequency deviations as well as rates of change of frequency (RoCoF) following abrupt power losses. The magnitude of RoCoF's and frequency deviations strongly depend on the fault location, and we find the largest effects for faults located on the support of the slowest mode-the Fiedler mode-of the network Laplacian matrix. This mode essentially vanishes over Belgium, Eastern France, Western Germany, northern Italy and Switzerland. Buses inside these regions are only weakly affected by faults occuring outside. Conversely, faults inside these regions have only a local effect and disturb only weakly outside buses. Following this observation, we reduce rotational inertia through three different procedures by either (i) reducing inertia on the Fiedler mode, (ii) reducing inertia homogeneously and (iii) reducing inertia outside the Fiedler mode. We find that procedure (iii) has little effect on disturbance propagation, while procedure (i) leads to the strongest increase of RoCoF and frequency deviations. This shows that, beyond absorbing frequency disturbances following nearby faults, inertia also mitigates frequency disturbances from distant power losses, provided both the fault and the inertia are located on the support of the slowest modes of the grid Laplacian. These results for our model of the European transmission grid are corroborated by numerical investigations on the ERCOT transmission grid.

Dataset Information

The GPCR Network: a large-scale collaboration to determine human GPCR structure and function.

Publications

The GPCR Network: a large-scale collaboration to determine human GPCR structure and function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets