Computational Simulation of Aptamer–Protein Interactions Using AptaDock: A Case Study on CD47 Inhibition in Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is an aggressive brain cancer that originates in the glial cells of the brain. It is the most common malignant brain cancer in adults. CD47 is a transmembrane protein that is overex- pressed in several cancers, including glioblastoma multiforme (GBM), where it plays a key role in tumor immune evasion by delivering a ’don’t eat me’ signal to macrophages via the SIRPα receptor. In GBM, ele- vated CD47 expression has been correlated with poor prognosis and resistance to immune clearance, mak- ing it a promising therapeutic target. Aptamers—short, single-stranded DNA or RNA molecules—have gained increasing recognition for their high specificity and affinity for target molecules. Aptamer-protein affinity studies have revealed promising interactions with biotechnology and molecular medicine appli- cations. In this research work, we have developed a pipeline to select an appropriate aptamer for treating GBM. We hypothesize that aptamer s63 interacts strongly with the predicted binding site of the CD47 receptor and could be used to inhibit the multiplication of GBM cells. We have utilized computational methods, such as AlphaFold 3, to indicate the 3D structure of the CD47 receptor. We have also employed molecular docking simulations using the HDOCK software to investigate the interactions between CD47 receptors and aptamers. The molecular docking simulation shows that the CD47-aptamer complex s66 formed the most hydrogen bonds and salt bridges. On this basis, aptamer s66 was selected as the most appropriate aptamer candidate. The current research will help design novel treatment strategies for GBM and aid in mitigating the global burden of the disease.