Song Wei, Jing Zhifeng, Meng Lijun, Zhou Ruhong
Institute of Quantitative Biology, Zhejiang University, Hangzhou 310027, China.
IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598, United States.
ACS Omega. 2020 May 8;5(19):11005-11012. doi: 10.1021/acsomega.0c00822. eCollection 2020 May 19.
Tungsten oxide nanodot (WO ) is an active photothermal nanomaterial that has recently been discovered as a promising candidate for tumor theranostics and treatments. However, its potential cytotoxicity remains elusive and needs to be evaluated to assess its biosafety risks. Herein, we investigate the interactions between WO and two ubiquitous protein domains involved in protein-protein interactions, namely, WW and SH3 domains, using atomistic molecular dynamics simulations. Our results show that WO interacts only weakly with the key residues at the putative proline-rich motif (PRM) ligand-binding site of both domains. More importantly, our free energy landscape calculations reveal that the binding strength between WO and WW/SH3 is weaker than that of the native PRM ligand with WW/SH3, implying that WO has a limited inhibitory effect over PRM on both the WW and SH3 domains. These findings suggest that the cytotoxic effects of WO on the key modular protein domains could be very mild, which provides new insights for the future potential biomedical applications of this nanomaterial.
氧化钨纳米点（WO）是一种活性光热纳米材料，最近被发现是肿瘤诊疗和治疗的一个有前景的候选材料。然而，其潜在的细胞毒性仍然难以捉摸，需要进行评估以评估其生物安全风险。在此，我们使用原子分子动力学模拟研究了WO与参与蛋白质-蛋白质相互作用的两个普遍存在的蛋白质结构域（即WW和SH3结构域）之间的相互作用。我们的结果表明，WO与这两个结构域假定的富含脯氨酸基序（PRM）配体结合位点的关键残基仅存在微弱相互作用。更重要的是，我们的自由能景观计算表明，WO与WW/SH3之间的结合强度弱于天然PRM配体与WW/SH3之间的结合强度，这意味着WO对PRM在WW和SH3结构域上的抑制作用有限。这些发现表明，WO对关键模块化蛋白质结构域的细胞毒性作用可能非常轻微，这为这种纳米材料未来潜在的生物医学应用提供了新的见解。
