Modeling the 3D structure of GPCRs from sequence

G‐protein‐coupled receptors (GPCRs) are a large and functionally diverse protein superfamily, which form a seven transmembrane (TM) helices bundle with alternating extra‐cellular and intracellular loops. GPCRs are considered to be one of the most important groups of drug targets because they are inv...

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Published inMedicinal research reviews Vol. 21; no. 5; pp. 472 - 483
Main Authors Shacham, Sharon, Topf, Maya, Avisar, Noa, Glaser, Fabian, Marantz, Yael, Bar-Haim, Shay, Noiman, Silvia, Naor, Zvi, Becker, Oren M.
Format Journal Article Conference Proceeding
LanguageEnglish
Published New York John Wiley & Sons, Inc 01.09.2001
Wiley
Subjects
Amino Acid Sequence
Animals
Biological and medical sciences
Drug Design
General pharmacology
GPCR
GTP-Binding Proteins - chemistry
Humans
Medical sciences
modeling
Models, Structural
Pharmacology. Drug treatments
Physicochemical properties. Structure-activity relationships
Protein Conformation
Receptors, Cell Surface - chemistry
structure based drug discovery
Human
Membrane protein
Clinical chemistry
Review
Modeling
Chemotherapy
Treatment
Three dimensional structure
Scientific research
Adult
Technique
G protein
Biological receptor
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Summary:G‐protein‐coupled receptors (GPCRs) are a large and functionally diverse protein superfamily, which form a seven transmembrane (TM) helices bundle with alternating extra‐cellular and intracellular loops. GPCRs are considered to be one of the most important groups of drug targets because they are involved in a broad range of body functions and processes and are related to major diseases. In this paper we present a new technology, named PREDICT, for modeling the 3D structure of any GPCR from its amino acid sequence. This approach takes into account both internal protein properties (i.e., the amino acid sequence) and the properties of the membrane environment. Unlike competing approaches, the new technology does not rely on the single known structure of rhodopsin, and is thus capable of predicting novel GPCR conformations. We demonstrate the capabilities of PREDICT in reproducing the known experimental structure of rhodopsin. In principle, PREDICT‐generated models offer new opportunities for structure‐based drug discovery towards GPCR targets. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 472–483, 2001
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ISSN:0198-6325
1098-1128
DOI:10.1002/med.1019