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.

随着二硫化钼（MoS ₂）在生物医学中的广泛应用，其与生物分子的作用机理已引起越来越多的关注。在此，进行分子动力学模拟以研究MoS ₂纳米管对信号蛋白YAP65（一种重要的Yes激酶相关蛋白结构域（WW域））与富含脯氨酸的基序配体（PRM）的结合的影响。我们基于WW域，PRM和MoS ₂纳米管之间不同的初始结合模式设计了四个系统，并观察到两种影响WW域与PRM结合的方式。第一个途径是WW域中的活动位点被MoS ₂占据纳米管，可防止WW域绑定到PRM。在第二种途径中，WW结构域用残基W17和F29而不是两个高度保守的残基（Y28和W39）与PRM结合，形成不稳定的组合。这两个结果可能导致WW域失去其原始功能或传递错误的信号。然而，MoS ₂纳米管并没有破坏复合材料中WW域和PRM的结构和结合。这些发现揭示了MoS ₂纳米管与信号蛋白系统之间的相互作用，同时为MoS ₂纳米管的潜在纳米毒性提供了另一有价值的见解。