Letter to the Editor: Quercetin and taxifolin completely break MDM2-p53 association: molecular dynamics simulation study by S. Verma, A. Singh, A. Mishra. Med Chem Res 2013, 22(6) 2778–2787

Abstract

In their contribution Verma et al. propose a drastic anti-cancer effect of quercetin and taxifolin based on molecular dynamics (MD) simulations of the MDM2-p53 protein complex bound to a ligand. However, we have severe concerns that the observed dissociation of the MDM2-p53 complex is not caused by ligand interaction, but an artifact arising from technical issues of post-processing the simulation data. This becomes evident from the root-mean-square deviation plots versus time of the two ligand-bound protein complex simulations, where huge and immediate jumps indicate analysis problems. In order to corroborate our view, we performed MD simulations of the MDM2-p53 complex without any ligand, which is experimentally known to be stable. We observed similar pseudo-dissociation events in the raw MD data that disappeared after proper post-processing. Thus, we strongly recommend a careful re-analysis of the original raw MD data by the authors. Although we do not exclude a dissociative effect of quercetin and taxifolin onto MDM2-p53, and therefore, potential anti-cancer properties of those compounds, the effect seen in the MD simulations should be much more subtle on that timescale.