Specificities of Protein Homology Modeling for Allosteric Drug Design.
Allosteric drugs
Allosteric modulators
GPCRs
Homology modeling
Potassium ion channels
Journal
Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969
Informations de publication
Date de publication:
2023
2023
Historique:
entrez:
24
3
2023
pubmed:
25
3
2023
medline:
28
3
2023
Statut:
ppublish
Résumé
The allosteric binding sites are usually located in the flexible areas of proteins, which are hardly visible in the crystal structures. However, there are notable exceptions like allosteric sites in receptors in class B and C of GPCRs, which are located within a well-defined bundle of transmembrane helices. Class B and C evolved from class A and even after swapping of orthosteric and allosteric sites the central binding site persisted and it can be used for easy design of allosteric drugs. However, studying the ligand binding to the allosteric sites in the most populated class A of GPCRs is still a challenge, since they are located mostly in unresolved parts of the receptor's structure, and especially N-terminus. This chapter provides an example of cannabinoid CB1 receptor N-terminal homology modeling, ligand-guided modeling of the allosteric site in GABA receptor, as well as C-linker modeling in the potassium ion channels where the allosteric phospholipid ligand PIP2 is bound.
Identifiants
pubmed: 36959457
doi: 10.1007/978-1-0716-2974-1_19
doi:
Substances chimiques
Ligands
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
339-348Informations de copyright
© 2023. Springer Science+Business Media, LLC, part of Springer Nature.
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