Target Binding of Black Phosphorus Nanomaterial to Polo‐Like Kinase 1 for Cancer Chemotherapy: A Mutual Selection of Nanomaterial and Protein

The intrinsic properties of black phosphorus (BP) nanomaterials (NMs) enable them for targeted binding to polo-like kinase 1 (PLK1), thus inhibiting its kinase activity. However, the mechanism and targeted binding sites underlying this interaction remain unclear. To elucidate the critical properties of PLK1 that facilitate its interaction with BPNMs, the binding ability of BPNMs was compared across PLK family proteins. Although BPNMs exhibited a weak binding affinity for PLK3, PLK1 demonstrated the most favorable physicochemical properties for its binding. Factors as surface charge, hydrophobicity, secondary and three-dimensional structures significantly affected the interaction of PLK family proteins to BPNMs. The binding affinity was primarily determined by amino acid residues at the binding interface, where arginine and proline played critical roles in mediating the interaction of BPNMs-PLK1. BPNMs inhibited PLK1 activation by binding to key residues of the kinase domain, including S49, Y203, D204, E206, and R207. In conclusion, this study elucidates the molecular basis of the specific interaction between BPNMs and PLK1, highlighting the pivotal role of the amino acid residues in NM-protein binding. This work demonstrates that NM-protein interactions are a mutual selection and driven by the physicochemical properties of both proteins and NMs.