Digital Diagnostics: In Silico Design of Aptamers for Early Alzheimer’s Detection via PDGFR-β Binding
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and neuronal dysfunction. Early diagnosis is critical for improving patient outcomes, yet current detection methods remain limited in sensitivity and accessibility. Platelet-derived growth factor receptor beta (PDGFR-β), a biomarker linked to blood–brain barrier integrity and neurovascular dysfunction, has emerged as a promising target for early AD detection. In this study, we employed an in silico approach to design and evaluate aptamers with high binding affinity for PDGFR-β. Protein structures were modeled using UniProt and AlphaFold, and potential binding sites were predicted with ScanNet, identifying the D2 extracellular domain as the most favorable target. Molecular docking simulations were performed with HDOCK, followed by detailed interaction profiling using PLIP and RinMaker. Binding free energies were calculated with PRODIGY to assess thermodynamic stability. The results demonstrated stable interactions, including hydrogen bonding, hydrophobic contacts, and salt bridges, with favorable ΔG values supporting strong aptamer–protein binding. These findings highlight the feasibility of computationally designed aptamers as diagnostic probes for PDGFR-β, providing a cost-effective and rapid approach for early-phase research. While experimental validation is required to confirm specificity and stability in biological systems, this work establishes a foundation for aptamer-based biosensors and diagnostic assays aimed at enabling earlier detection of AD.
Medulloblastomas are fast-growing, malignant brain tumors that originate in the cerebellum and primarily affect children. Recently, dihydrolipoyl transacetylase (DLAT) has been identified as a novel therapeutic target in medulloblastomas and may also hold potential for the treatment of childhood medulloblastoma. Elevated expression of DLAT sensitizes Group-3 medulloblastoma cells to copper-induced cell death (cuproptosis), leading to suppression of the oncogene c-Myc and a subsequent reduction in tumor growth. Therefore, inhibition of DLAT may reduce the susceptibility of Group-3 medulloblastoma cells to cuproptosis, potentially sustaining c-Myc-driven tumor proliferation. We hypothesize that Ligand I binds strongly to the DLAT protein and could be used to inhibit its function, thereby suppressing the proliferation of medulloblastoma cells. In this work, we employed computational strategies, including protein modeling, virtual screening, and chemical mutations, to predict inhibitors that can bind to the DLAT protein. From the simulations, we have identified five chemical compounds that bind strongly to the predicted binding site of the protein. Finally, we have also performed chemical mutations on the ligands, and the ADMET properties of the compounds have been identified. Our research and conclusions may inform the design of a future drug that targets the DLAT protein, which in turn reduces c-MYC and Medulloblastomas.