Abstract
Tungsten oxide nanodot (WO(3-x) ) 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(3-x) 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(3-x) 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(3-x) and WW/SH3 is weaker than that of the native PRM ligand with WW/SH3, implying that WO(3-x) has a limited inhibitory effect over PRM on both the WW and SH3 domains. These findings suggest that the cytotoxic effects of WO(3-x) on the key modular protein domains could be very mild, which provides new insights for the future potential biomedical applications of this nanomaterial.