Computational Molecular Docking Simulations of Aptamers Targeting CD30 in the Treatment of Hodgkin Lymphoma

Hodgkin’s lymphoma is a malignancy (cancer) that affects the immune system, primarily lymphocytes (white blood cells). CD30 is a protein receptor expressed on the surface of Hodgkin's cancer cells and is a crucial target for diagnosis and treatment. As of now, current CD30-targeted therapies come with extensive side effects like peripheral neuropathy, myelosuppression, and hepatic and pulmonary toxicities. Typically, the body uses Natural Killer (NK) white blood cells to control tumors and limit their spread. Still, NK cells require prior exposure to a specific pathogen and, therefore, cannot be used for targeted cancer treatment. In response, Yang et al. designed aptamers (RNA/DNA molecules) anchored to the surface of NK cells to target the CD30 receptors of Hodgkin cancer cells. In this research experiment, computational modeling of aptamers targeting CD30 receptors was simulated. Specifically, molecular docking simulations using the HDOCK software were conducted to identify aptamers that can be used as biomarkers or targeted therapies for Hodgkin lymphoma. The docked results show that the aptamer Apt3 binds strongly to Domain 3 of the CD30 receptor. These results were further validated using the graph neural network method. Additionally, a complete CD30 receptor structure was modeled using AlphaFold 3, which showed that the receptor has complex extracellular cysteine-rich domains involved in the ligand binding. It can be assumed that these cysteine-rich domains could encourage the aptamer to bind to the CD30 receptor. These results will help develop NK cell aptamer-based CD30 targeted therapies for Hodgkin lymphoma.