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Modeling and Deorphanization of Orphan GPCRs

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Computational Methods for GPCR Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1705))

Abstract

Despite tremendous efforts, approximately 120 GPCRs remain orphan. Their physiological functions and their potential roles in diseases are poorly understood. Orphan GPCRs are extremely important because they may provide novel therapeutic targets for unmet medical needs. As a complement to experimental approaches, molecular modeling and virtual screening are efficient techniques to discover synthetic surrogate ligands which can help to elucidate the role of oGPCRs. Constitutively activated mutants and recently published active structures of GPCRs provide stimulating opportunities for building active molecular models for oGPCRs and identifying activators using virtual screening of compound libraries. We describe the molecular modeling and virtual screening process we have applied in the discovery of surrogate ligands, and provide examples for CCKA, a simulated oGPCR, and for two oGPCRs, GPR52 and GPR34.

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  1. Research Informatics, Evotec (France) SAS, 195 Route d’Espagne, 31036, Toulouse, France

    Constantino Diaz, Patricia Angelloz-Nicoud & Emilie Pihan

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  1. Constantino Diaz
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  2. Patricia Angelloz-Nicoud
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  3. Emilie Pihan
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Correspondence to Constantino Diaz .

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  1. Evotec (UK) Ltd., Abingdon, Oxfordshire, United Kingdom

    Alexander Heifetz

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Diaz, C., Angelloz-Nicoud, P., Pihan, E. (2018). Modeling and Deorphanization of Orphan GPCRs. In: Heifetz, A. (eds) Computational Methods for GPCR Drug Discovery. Methods in Molecular Biology, vol 1705. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7465-8_21

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  • DOI: https://doi.org/10.1007/978-1-4939-7465-8_21

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