The Glycine Receptor Allosteric Ligands Library (GRALL)

Author:

Cerdan Adrien H12,Sisquellas Marion1,Pereira Gilberto1,Barreto Gomes Diego E3,Changeux Jean-Pierre45,Cecchini Marco1ORCID

Affiliation:

1. Institut de Chimie de Strasbourg, UMR7177, CNRS, Université de Strasbourg, F-67083 Strasbourg Cedex, France

2. Channel-Receptors Unit, Institut Pasteur, 75015 Paris, France

3. Diretoria de Metrologia Aplicada às Ciências da Vida-Instituto Nacional de Metrologia, Qualidade e Tecnologia, Duque de Caxias 25.250-020, Brazil

4. CNRS, URA 2182, F-75015, Collège de France, F-75005 Paris, France

5. Kavli Institute for Brain & Mind, University of California San Diego, La Jolla, CA 92093, USA

Abstract

Abstract Motivation Glycine receptors (GlyRs) mediate fast inhibitory neurotransmission in the brain and have been recognized as key pharmacological targets for pain. A large number of chemically diverse compounds that are able to modulate GlyR function both positively and negatively have been reported, which provides useful information for the development of pharmacological strategies and models for the allosteric modulation of these ion channels. Results Based on existing literature, we have collected 218 unique chemical entities with documented modulatory activities at homomeric GlyR-α1 and -α3 and built a database named GRALL. This collection includes agonists, antagonists, positive and negative allosteric modulators and a number of experimentally inactive compounds. Most importantly, for a large fraction of them a structural annotation based on their putative binding site on the receptor is provided. This type of annotation, which is currently missing in other drug banks, along with the availability of cooperativity factors from radioligand displacement experiments are expected to improve the predictivity of in silico methodologies for allosteric drug discovery and boost the development of conformation-based pharmacological approaches. Availability and implementation The GRALL library is distributed as a web-accessible database at the following link: https://ifm.chimie.unistra.fr/grall. For each molecular entry, it provides information on the chemical structure, the ligand-binding site, the direction of modulation, the potency, the 3D molecular structure and quantum-mechanical charges as determined by our in-house pipeline. Contact mcecchini@unistra.fr Supplementary information Supplementary data are available at Bioinformatics online.

Funder

French National Research Agency

European Union’s Horizon 2020 Framework Program for Research and Innovation

Ecole Doctorale des Sciences Chimiques

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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