Ligand Docking Methods to Recognize Allosteric Inhibitors for G-Protein-Coupled Receptors
K Harini1, S Jayashree2,3, Vikas Tiwari1
1Department of Bioinformatics, National Centre for Biological Sciences, Bangalore, India.
Bioinformatics and Biology Insights
|November 4, 2021
Summary
G-protein-coupled receptors (GPCRs) are key drug targets, but nonspecific binding causes side effects. Computational docking reveals that ligands can bind to diverse allosteric sites, offering new strategies for targeted drug development.
Area of Science:
- Biochemistry
- Pharmacology
- Computational Biology
Background:
- G-protein-coupled receptors (GPCRs) are crucial membrane proteins involved in numerous cellular functions and represent significant drug targets.
- Current GPCR-targeting drugs, despite FDA approval, often exhibit side effects due to non-specific drug binding.
Purpose of the Study:
- To investigate the diversity of ligand binding sites within GPCRs using computational docking.
- To explore alternative binding sites beyond conserved regions for improved drug specificity.
Main Methods:
- Utilized computational docking simulations to analyze the interactions between GPCRs and their cognate ligands.
- Examined known ligand-GPCR complex structures to identify binding site variations.
Main Results:
- Identified that cognate ligands can dock at allosteric binding sites with higher affinity than at conserved sites for certain GPCRs.
- Observed that amino acid residues in these specific allosteric binding sites are not conserved across different GPCR subfamilies.
Conclusions:
- Computational docking can reveal previously unrecognized allosteric binding sites in GPCRs.
- This approach aids in predicting specific allosteric binders, potentially leading to drugs with reduced side effects.
More Related Videos
09:03Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
Published on: March 10, 2020
12.9K
08:49Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
616
Related Concept Videos
01:15G Protein-coupled Receptors
14.0K
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...
14.0K
00:49Ligand Binding and Linkage
5.1K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.1K
02:40Ligand Binding Sites
14.2K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
14.2K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.0K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.0K
01:58Cooperative Allosteric Transitions
2.4K
2.4K
01:08Allosteric Regulation
61.0K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
61.0K