Related Experiment Video
Updated: May 31, 2026
08:46
A "Dual-Addition" Calcium Fluorescence Assay for the High-Throughput Screening of Recombinant G Protein-Coupled Receptors
Published on: December 2, 2022
G-protein coupled receptors virtual screening using genetic algorithm focused chemical space.
Carleton Sage1, Runtong Wang, Gareth Jones
1Computational Systems, Arena Pharmaceuticals, San Diego, California 92121, USA. csage@arenapharm.com
Journal of Chemical Information and Modeling
|July 19, 2011
Summary
A new method, GAFDAS, improves ligand-based virtual screening (LBVS) for G-protein coupled receptors (GPCRs). It uses a genetic algorithm to select focused descriptors, enhancing the early identification of potential drug compounds.
Area of Science:
- Computational chemistry
- Drug discovery
- Bioinformatics
Background:
- Ligand-based virtual screening (LBVS) leverages compound activity data for target identification.
- G-protein coupled receptors (GPCRs) are crucial drug targets, necessitating efficient screening methods.
- Existing methods face challenges in handling large, complex datasets.
Purpose of the Study:
- To develop an advanced LBVS method for GPCRs.
- To enhance screening collection and facilitate hit expansion.
- To improve the selection of active compounds from large databases.
Main Methods:
- Implemented a modified descriptor selection method (rBDACCS) by removing correlated descriptors.
- Extended rBDACCS with a genetic algorithm (GA) for target-specific descriptor selection, creating GAFDAS.
- Validated GAFDAS and rBDACCS using 252 GPCR/ligand sets against decoy databases.
Main Results:
- Both rBDACCS and GAFDAS demonstrated effectiveness in LBVS.
- GAFDAS consistently outperformed rBDACCS in the early selection of active compounds.
- The genetic algorithm approach optimized descriptor sets for improved screening performance.
Conclusions:
- GAFDAS offers a superior approach for LBVS, particularly for GPCR targets.
- Target-specific descriptor selection via genetic algorithms enhances compound identification accuracy.
- The developed method holds significant potential for accelerating drug discovery efforts.
Related Concept Videos
01:15G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
01:15G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
02:46Genetic Screens
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
01:30Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...