The Glycine Receptor Allosteric Ligands Library (GRALL)

Area of Science:

• Pharmacology and Neuroscience
• Computational Chemistry
• Drug Discovery

Background:

• Glycine receptors (GlyRs) are crucial for inhibitory neurotransmission and are key targets for pain management.
• Numerous compounds modulating GlyR function exist, offering potential for therapeutic strategies.
• Understanding allosteric modulation of these ion channels is vital for drug development.

Purpose of the Study:

• To create a comprehensive database of chemical entities modulating GlyRs.
• To provide structural annotations of binding sites for improved in silico drug discovery.
• To facilitate the development of conformation-based pharmacological approaches for GlyR targets.

Main Methods:

• Compiled a database (GRALL) of 218 unique chemical entities with documented modulatory activities at GlyR-α1 and -α3.
• Included agonists, antagonists, positive and negative allosteric modulators, and inactive compounds.
• Provided structural annotations for putative binding sites and cooperativity factors.

Main Results:

• The GRALL database contains 218 compounds with diverse modulatory activities at GlyR-α1 and -α3.
• Structural annotations and cooperativity factors are provided for a significant fraction of compounds.
• The database is accessible online and includes chemical structure, binding site, modulation direction, potency, and 3D molecular data.

Conclusions:

• The GRALL database enhances in silico methodologies for allosteric drug discovery.
• It supports the development of conformation-based pharmacological approaches for GlyR targets.
• GRALL serves as a valuable resource for researchers in pain management and neuroscience.