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Non-destructive Inhibition of Metallofullerenol [email protected](OH)22 on WW domain: Implication on Signal Transduction Pathway

Authors
Journal
Scientific Reports
2045-2322
Publisher
Nature Publishing Group
Publication Date
Volume
2
Identifiers
DOI: 10.1038/srep00957
Keywords
  • Article
Disciplines
  • Biology

Abstract

Endohedral metallofullerenol [email protected](OH)22 has recently been shown to effectively inhibit tumor growth; however, its potential adverse bioeffects remain to be understood before its wider applications. Here, we present our study on the interaction between [email protected](OH)22 and WW domain, a representative protein domain involved in signaling and regulatory pathway, using all-atom explicit solvent molecular dynamics simulations. We find that [email protected](OH)22 has an intrinsic binding preference to the binding groove, particularly the key signature residues Y28 and W39. In its binding competition with the native ligand PRM, [email protected](OH)22 is shown to easily win the competition over PRM in occupying the active site, implying that [email protected](OH)22 can impose a potential inhibitory effect on the WW domain. Further analyses with binding free energy landscapes reveal that [email protected](OH)22 can not only directly block the binding site of the WW domain, but also effectively distract the PRM from its native binding pocket.

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