An operational model for GPCR homodimers and its application in the analysis of biased signaling.

G-protein-coupled receptors are one of the most important protein superfamilies as drug targets in drug discovery programs. Their interactions with ligands are influenced by their homomerization. In this study, we propose an operational model for receptor homodimers, which includes constitutive receptor activity. Distinct functional response curves can be obtained from this model, which can satisfactorily depict typical complex experimental data as biphasic and bell-shaped curves. Operational parameters in the model can provide mechanistic explanations for observed functional complexity associated with the cooperativity and intrinsic efficacy of ligands. Because the model presented here is derived from the conceptual framework of operational models, it takes advantage of the body of knowledge coming from the widespread use of this type of modeling. The operational homodimer model can also explain the biased signaling dependent on ligand concentration. In conclusion, this operational homodimer model has a wide range of applications in pharmacological research.

• Publication year

  2018

• Venue

  Drug Discovery Today

• Publication date

  2018-09-01

• Fields of study

  Biology, Medicine, Chemistry, Computer Science

• Identifiers
  DOI 10.1016/j.drudis.2018.04.004PMID 29649573
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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