Exploring potential GPR55 agonists using virtual screening, molecular docking and dynamics simulation studies

• Published in: Journal of biomolecular structure & dynamics 2024-12, p.1
• Main Authors: Garisetti, Vasavi, Varughese, Roslin Elsa, Anandamurthy, Arthikasree, Haribabu, Jebiti, Dasararaju, Gayathri
• Format: Article
• Language: English
• ISSN: 1538-0254

GPR55, an orphan GPCR, holds significance in the context of neurological disorders and its activation is important for regulating neurological responses. This has led us to uncover and explore a set of ligands which may act as potential agonists. We have predicted the GPR55 structural model followed by molecular docking, dynamics simulation studies, free energy landscape and MMPBSA analyses to study the dynamic nature of GPR55 in the presence of different ligands. We initially carried out structure-based virtual screening of a dataset from ChemDiv Database against the GPR55 model. Based on the docking results, it was observed that thiazole and triazole derivatives were present among the top hits and notably, two compounds - one thiazole (lead1) and one triazole (lead2) derivative were shortlisted. In addition, as we are working on the design, synthesis, structural and functional properties of several thiazole and triazole compounds, we have attempted to study the binding potential of two compounds SVS1 (thiazole derivative) and SVS2 (triazole derivative) with GPR55. The synthesis and structural aspects of SVS1 and SVS2 were previously reported by our team. Further, we have included a known agonist O-1602 in the present study for comparative analysis. All the compounds showed promising interactions with GPR55 during molecular dynamics simulations. Our findings suggest that lead1, lead2, SVS1 and SVS2 have the potential to serve as GPR55 agonists and the study throws light on the importance of thiazole and triazole moieties in the ligands. This offers a promising avenue for the development of new therapies for neurological disorders.