Molecular Docking and Molecular Dynamics Approaches to Evaluate the Specificity of the AS1411–Lapatinib Aptamer Complex in HER2-Positive Breast Cancer

HER2-positive breast cancer is an aggressive subtype characterized by the overexpression of the HER2 tyrosine kinase receptor, which promotes uncontrolled cell proliferation and tumor progression. Lapatinib is a dual EGFR/HER2 inhibitor widely used in targeted therapies; however, its limited bioavailability and adverse effects associated with systemic distribution highlight the need for more selective molecular targeting strategies. In this context, DNA aptamers have emerged as promising platforms for specific molecular recognition and the development of targeted drug delivery systems.

The AS1411 aptamer, which is rich in guanine regions and capable of adopting stable conformational structures, represents a potential candidate for the selective transport of therapeutic agents. As an initial step in the structural design of the aptamer–drug complex, multiple conformations of the ligand Lapatinib were generated in order to represent its molecular flexibility and obtain energetically favorable geometries for subsequent interaction studies.

Additionally, potential binding cavities were identified using structural site detection algorithms. The analysis revealed seven possible interaction sites, with Site 1 identified as the main cavity, showing a size of 78, a PLB value of 1.54, and 10 hydrophobic features, associated with 62 nucleotide residues, including DG9, DT10, DT11, DG12, DT13, DG15, DT16, DG17, DG18, DG26, DG27, and DT28. These characteristics suggest a structurally favorable region for interactions with aromatic ligands.

The results obtained establish a structural basis for subsequent molecular docking studies and molecular dynamics simulations aimed at evaluating the stability of the AS1411–Lapatinib complex and its potential application in targeted delivery strategies for HER2-positive breast cancer.