Phosphorene has recently shown promise as a two-dimensional (2D) nanomaterial to overcome shortcomings (such as zero band gap and low carrier mobility) of similar 2D nanomaterials like graphene and transition metal dichalcogenides. Interest in the application of this novel material has recently exploded within the biomedical field, and the need to evaluate phosphorene's biocompatibility is becoming more and more urgent. In the present study, large scale molecular dynamics (MD) simulations were performed in order to investigate the interactions of phosphorene with signal protein WW domain ubiquitous in protein-protein interactions and signaling transduction. It was found that, among the various contact orientations of protein on the surface of phosphorene, two types of disruption to the signal protein were exhibited. The first disruption was phosphorene snatching the ligand PRM from WW domain followed by subsequent blocking of the active site, however the structure of the protein was conserved. The second involved the tearing of the β-sheet in the WW domain resulting in the collapse of the protein's secondary structure, although PRM could still bind to the active sites of WW domain. Importantly, the signal protein lost its native function regardless of disruption type (destroying or snatching). The two models of signal disruption showcase new pathways for adjusting protein-nanomaterial interactions. The findings presented here provide valuable insights on the biocompatibility of phosphorene and will prove important in the design of biosensors based on this exciting nanomaterial.