Assessment of Phage-Displayed Peptides Targeting Cancer Cell Surface Proteins: A Comprehensive Molecular Docking Study

Peptides binding overexpressed breast and cervical cancer cell surface proteins can be isolated by phage display technology, and their affinity to their potential receptors can be assessed by molecular docking. We isolated 44 phage clones displaying dodecapeptides with high affinity to HeLa cervical cancer and MDA-MB-231 (MDA) breast cancer cells by repeated biopanning of an MK13 phage library and explored their affinity to specific proteins by molecular docking. Six peptides appeared repeatedly during biopanning: two with affinity to HeLa (H5/H21), and four with affinity to MDA cells (M3/M7/M15/M17). Peptide pairs M3/H5 and H1/M17 had affinity to both cell lines. A systematic review identified Annexin A2, EGFR, CD44, CD146, and Integrin alpha V as potential protein targets in HeLa cells, and Vimentin, Galectin-1, and Annexins A1 and A5 in MDA cells. Via virtual screening, we selected six peptides with the highest total docking scores: H1 (−916.32), H6 (−979.21), H19 (−1093.24), M6 (−732.21), M16 (−745.5), and M19 (−739.64), and identified that docking scores were strengthened by the protein type, the interacting amino acid side chains, and the polarity of peptides. This approach facilitates the selection of relevant peptides that could be further explored for active targeting in cancer diagnosis and treatment.