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References

Nemoto W, Yamanishi Y, Limviphuvadh V, Saito A, Toh H. GGIP: Structure and sequence-based GPCR-GPCR interaction pair predictor. Proteins. 2016 Sep;84(9):1224-33. PubMed PMID: 27191053.

Summary

G Protein-Coupled Receptors (GPCRs) are important pharmaceutical targets. More than 30% of currently marketed pharmaceutical medicines target GPCRs. Numerous studies have reported that GPCRs function not only as monomers but also as homo- or hetero-dimers or higher-order molecular complexes. Many GPCRs exert a wide variety of molecular functions by forming specific combinations of GPCR subtypes. In addition, some GPCRs are reportedly associated with diseases. biochemical and biological functions of various combinations of hetero oligomers have not been clarified. GPCR oligomerization is now recognized as an important event in various biological phenomena, and many researchers are investigating this subject. We have developed a support vector machine (SVM)-based method to predict interacting pairs for GPCR oligomerization, by integrating the structure and sequence information of GPCRs. The performance of our method was evaluated by the Receiver Operating Characteristic (ROC) curve. The corresponding area under the curve was 0.938. As far as we know, this is the only prediction method for interacting pairs among GPCRs. Our method could accelerate the analyses of these interactions, and contribute to the elucidation of the global structures of the GPCR networks in membranes. We launched a web service to predict the interacting pairs for GPCR oligomerization on this server. To our knowledge, it is the only web service that predicts the interacting pairs for GPCR oligomerization. It will be useful to investigate molecular functions of GPCR oligomers and molecular network via GPCRs. GGIP website is free and open to all users, and there is no login requirement.

Usage

Input the query GPCR 1 amino acid sequence in FASTA format.
Input the query GPCR 2 amino acid sequence in FASTA format.
Select the PDB ID of a structure for query GPCR 1.
Select the PDB ID of a structure for query GPCR 2.
Press the submit button.

Examples

Table 1. Query candidates and parameters for GGIP execution.

No.	Accession Number 1	Protein Name 1	Adopted Structure 1: PDB ID 1	Accession Number 2	Protein Name 2	Adopted Structure 2: PDB ID	Prediction result
1	NP_000530.1	rhodopsin [Homo sapiens]	1L9H	NP_002554.1	P2Y purinoceptor 1 [Homo sapiens]	4NTJ	Non interaction pair
2	NP_000530.1	rhodopsin [Homo sapiens]	1L9H	NP_000530.1	rhodopsin [Homo sapiens]	1L9H	Interaction pair
3	NP_002554.1	P2Y purinoceptor 1 [Homo sapiens]	4NTJ	NP_002554.1	P2Y purinoceptor 1 [Homo sapiens]	4NTJ	Interaction pair

Contributors

Wataru Nemoto^1,², Shunsuke Fujishiro¹, Vachiranee Limviphuvadh³, Yoshihiro Yamanishi⁴, Motoaki Yamanoi¹, Sakie Shimamura¹, Aoi Fukushima², Hiroyuki Toh⁵

Graduate School of Science and Technology, Tokyo Denki University, Saitama, Japan
Department of Science and Technology, Tokyo Denki University, Saitama, Japan
Bioinformatics Institute, Agency for Science, Technology and Research, Singapore
Medical Institute of Bioregulation, Kyushu University, Japan
School of Science and Technology, Kwansei Gakuin University, Japan

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