Insect RDL Receptor Models for Virtual Screening: Impact of the Template Conformational State in Pentameric Ligand-Gated Ion Channels

FELSZTYNA, IVÁN; VILLARREAL, MARCOS A.; GARCÍA, DANIEL A.; MIGUEL, VIRGINIA

ACS Omega

American Chemical Society

Año: 2022 vol. 7 p. 1988 - 1988

he RDL receptor is one of the most relevant protein targets for insecticide molecules. It belongs to the pentameric ligand-gated ion channel (pLGIC) family. Given that the experimental structures of pLGICs are difficult to obtain, homology modeling has been extensively used for these proteins, particularly for the RDL receptor. However, no detailed assessments of the usefulness of homology models for virtual screening (VS) have been carried out for pLGICs. The aim of this study was to evaluate which are the determinant factors for a good VS performance using RDL homology models, specially analyzing the impact of the template conformational state. Fifteen RDL homology models were obtained based on different pLGIC templates representing the closed, open, and desensitized states. A retrospective VS process was performed on each model, and their performance in the prioritization of active ligands was assessed. In addition, the three best-performing models among each of the conformations w