Potential toxicity mechanism of MoS2 nanotube in the interaction between YAP65 WW domain and PRM

Abstract With the widespread application of Molybdenum disulfide (MoS2) in biomedicine, its mechanism of action with biomolecules has attracted increasing attention. Herein, molecular dynamics simulations were performed to investigate the effect of MoS2 nanotube on the binding of the signal protein YAP65, an important Yes kinase-associated protein domain (WW domain), to the proline rich motif ligand (PRM). We designed four systems based on the different initial binding modes among WW domain, PRM and MoS2 nanotube, and observed two ways to affect the binding of WW domain to PRM. The first pathway, the active site in WW domain was occupied by MoS2 nanotube, which prevents WW domain from binding to PRM. In the second pathway, WW domain was bound to PRM with residues W17 and F29 instead of the two highly conserved residues (Y28 and W39), forming an unstable combination. These two results might cause WW domain to lose its original function or to pass the mistaken signal. However, MoS2 nanotube did not destroy the structure and binding of WW domain and PRM in the composite. These findings shed light on the interaction between MoS2 nanotube and signal protein system, while providing another valuable insight into the potential nanotoxicity of MoS2 nanotube.