G Protein-Coupled Receptors: In silico Drug Discovery in 3D

The application of structure-based in silico methods to drug discovery is still considered a major challenge, especially when the x-ray structure of the target protein is unknown. Such is the case with human G protein-coupled receptors (GPCRs), one of the most important families of drug targets, whe...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-08, Vol.101 (31), p.11304-11309
Main Authors: Becker, Oren M., Marantz, Yael, Shacham, Sharon, Inbal, Boaz, Heifetz, Alexander, Kalid, Ori, Bar-Haim, Shay, Warshaviak, Dora, Fichman, Merav, Noiman, Silvia, Levitt, Michael
Format: Article
Language:English
Subjects:
Agonists
Algorithms
Binding Sites
Biological Sciences
Biophysics
Combinatorial Chemistry Techniques
Drug Design
Drug discovery
Drugs
Humans
In Vitro Techniques
Lead compounds
Libraries
Ligands
Modeling
Models, Chemical
Protein Structure, Quaternary
Proteins
Receptor, Serotonin, 5-HT1A - chemistry
Receptor, Serotonin, 5-HT1A - metabolism
Receptors
Receptors, CCR3
Receptors, Chemokine - chemistry
Receptors, Chemokine - metabolism
Receptors, Dopamine D2 - chemistry
Receptors, Dopamine D2 - metabolism
Receptors, G-Protein-Coupled - chemistry
Receptors, G-Protein-Coupled - metabolism
Receptors, Neurokinin-1 - chemistry
Receptors, Neurokinin-1 - metabolism
Receptors, Serotonin, 5-HT4 - chemistry
Receptors, Serotonin, 5-HT4 - metabolism
Serotonin receptors
Three dimensional imaging
Three dimensional modeling
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The application of structure-based in silico methods to drug discovery is still considered a major challenge, especially when the x-ray structure of the target protein is unknown. Such is the case with human G protein-coupled receptors (GPCRs), one of the most important families of drug targets, where in the absence of x-ray structures, one has to rely on in silico 3D models. We report repeated success in using ab initio in silico GPCR models, generated by the PREDICT method, for blind in silico screening when applied to a set of five different GPCR drug targets. More than 100,000 compounds were typically screened in silico for each target, leading to a selection of
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0401862101