Phosphorene, a novel two-dimensional material with a puckered surface morphology, has been considered a potentially better alternative to graphene for future applications. Therefore, it is important to evaluate and compare the biological responses of phosphorene and graphene. In this paper, with large scale molecular dynamics simulations, the villin headpiece (HP35) was used as a model protein to investigate the disruption of protein's structure (and function) caused by both phosphorene and graphene, for comparison of their biological responses. The results show that graphene's disruption to the structure of HP35 is more severe, indicating that phosphorene's interactions with HP35 are weaker as compared to graphene. Further analysis with two additional model materials, pseudo-phosphorene and pseudo-graphene, reveal that the puckered surface can have a significant effect in weakening the materials' ability to disrupt proteins. These findings might shed light on understanding/designing the protein-nanomaterial interactions and would be helpful for the bioapplications of the new nanomaterial, phosphorene.