ABS 031: Aptamer-Mediated Inhibition of Von Willebrand Factor (VWF) to Prevent Platelet Overactivation in Myocardial Ischemia-Reperfusion Injury: An In Silico Study

Alina Sohail ¹, Gaurav Sharma ²

¹ University of North Carolina at Chapel Hill, Chapel Hill, NC
² Eigen Sciences, Apex, NC

The Van Wickle Journal (2026) Volume 2, ABS031

Introduction: Myocardial ischemia-reperfusion injury occurs when blood returns to the heart after oxygen deprivation, often worsening cardiac damage through stress and inflammation. Von Willebrand Factor (VWF) binds to the GPIb-IX-V receptor on platelets, causing overactivation and vascular obstruction. Aptamers are short DNA or RN sequences designed to block such protein interactions. We hypothesize that aptamer A1 binds strongly to the predicted VWF binding site, preventing platelet overactivation. VWF and GPIb-IX-V were modeled with AlphaFold 3; aptamer structures were generated with UNAfold and FARFAR2. Docking and PLIP analysis showed A1 formed 12 hydrogen bonds and 4 salt bridges at the predicted site, while A2 formed 16 hydrogen bonds and 1 salt bridge. This is the first 3D structural model of GPIb-IX-V receptor in both VWF-bound and unbound states, highlighting aptamers’ potential in inhibiting VWF during myocardial ischemia-reperfusion injury.

Methods: A. Receptor Structure Modeling – Amino acids of the proteins were obtained from UniProt and modeled with AlphaFold 3. ScanNet was used to predict binding sites, and the Human Protein Atlas identified domains using UniProt ID P04275
B. Aptamer Structure Modeling – Aptamer sequences were folded into secondary structures using UNAfold, converted to dot-bracket notation in RNAStructure, and modeled in FARFAR2.
C. Molecular Docking Simulations and Analysis – Docking was performed using HDOCK, and complexes were analyzed with PLIP. Images were generated using ChimeraX and Canva.

Results: Aptamers A1 and A2 bound to VWF. A1 formed 12 hydrogen bonds and 4 salt bridges, while A2 formed 16 hydrogen bonds and 1 salt bridge. Since A1 binds to the predicted binding site, it was selected for further analysis. Electrostatic surface potential mapping revealed negatively charged aptamers binding to positive sites.

Discussion: This is the first structural clarification of the VWF-GPIb-V interaction, showing binding ot GPIba domains. Aptamer-based therapies are small and customizeable, making them a great treatment for cardiovascular conditions. Limitations include that this model is fully reliant on computational models. Aptamer A1 shows strong potential for preventing platelet overactivation, but in vivo and in vitro studies are necessary to confirm its safety.