Macromolecular Modeling Blog ™

G-protein coupled receptors comprise a large family of receptors that mediates signal transduction pathways. This family is extremely important and is the hub of drug discovery efforts. A recent market research reports that GPCR targeted drugs which now account for 25% of the pharmaceutical market are expected to increase market share to nearly 50% by 2012. While major pharma companies are increasingly entering into collaborations with GPCR platform development companies leading to pathbreaking drug discoveries. From the structural biology point of view it was just recently that a second crystal structure of a GPCR was solved, meaning that huge efforts are still necessary in modeling these important targets. To aid the ongoing efforts, we present a collection of online GPCR resources. 

Databases:

• IUPHAR Database of G Protein-Coupled Receptors - For each receptor you can find useful information such as a list of agonists and antagonists along side their affinities. Also features reports of recent pairings of receptors with endogenous or synthetic ligands.
• GPCRDB - An information system for G protein-coupled receptors. Among other information, offers mutational data, ligand binding data, lists cross references and offers a list of PDB files associated with GPCR’s.
• Swiss-Prot list of GPCR proteins
• GpDB - A relational database of G-proteins and their interactions with GPCRs and effector molecules. The sequences are classified according to a hierarchy of different classes, families and sub-families, based on extensive literature search.
• Endogenous GPCR List - This database lists the G protein coupled receptors expressed endogenously in various cell lines. 
• GPCR’s model database - Contains homology models of 907 GPCR’s from the human genome. Based on “Structure Modeling of All Identified G Protein–Coupled Receptors in the Human Genome” By Yang Zhang, Mark E. DeVries, Jeffrey Skolnick.
• GPCR natural variants DB - describes sequence variants within the family of human G Protein-Coupled Receptors.

Tools:

• PRED-GPCR - GPCRs Family classification from sequence alone. Based on a probabilistic method that uses family specific profile HMMs in order to determine to which GPCR family a query sequence belongs or resembles.
• PhyloFacts GPCR Phylogenomic Explorer - Contains 70 families and 2,535 Hidden Markov Models (family and subfamily). G-protein coupled receptor analysis, including phylogenetic tree construction and subfamily classification. Submit sequences for classification against the HMM library. 
• GPCR pattern recognition – a diagnostic resource for 7TM proteins. You may search a query sequence against the fingerprint database to determine if it belongs to one of the characterised superfamilies, families or receptor subtypes (~120 fingerprints are now available). You may scan either against the particular named fingerprint, or against the full PRINTS database; or use the interactive alignment editor (CINEMA) either simply to visualise or to augment alignments, as you desire.

Be Sociable, Share!

•