A Structure-Based in Silico Study Proposes Glycophorin-E as a Dual Target for Parkinson’s Disease and Alcohol Use Disorder Modulated by Oleuropein (OLE) Glycophorin-E: A Dual Target for PD/AUD via Oleuropein

Objective: Parkinson’s disease (PD) and alcohol use disorder (AUD) have different clinical profiles, but they may share certain molecular weaknesses. This computer-based study explores the new idea that Glycophorin-E (GYPE) could be a common target for both conditions, with the natural compound oleuropein (OLE) as a possible modulator. Methods: Using structure-based computational methods, we conducted molecular docking and interaction analysis to examine how OLE binds to a modeled GYPE structure. Results: The analysis showed that OLE has a stable and energetically favorable binding position in a proposed active site of GYPE, with a binding strength of -5.3 kcal/mol. The complex’s stability comes from a mix of specific intermolecular forces, including important hydrophobic interactions with Val35 and Tyr39, along with essential hydrogen bonds with Ser30, Thr36, Tyr39, and Gln43. Importantly, Tyr39 plays a dual role by also forming a stabilizing salt bridge, adding notable ionic interaction energy that helps stabilize the overall complex. These findings present the first computer-based evidence for strong and specific binding of OLE to GYPE. Conclusion: We suggest that this interaction could explain how OLE shows neuroprotective and anti-addictive effects by influencing GYPE-related pathways. However, this study has limitations since it is a computer-based analysis. Also, because Glycophorin E is a protein with low biological expression, further in vivo and in vitro studies are needed to confirm its potential effects in the body.