TY - JOUR
T1 - Insight into Interaction Mechanism of the Inhibitor pDI6W with MDM2 Based on Molecular Dynamics
AU - Chen , Jianzhong
AU - Liang , Zhi-Qiang
AU - Zhang , Qing-Gang
AU - Liu , Xiao-Yang
AU - Wang , Wei
AU - Liu , Jin-Qing
JO - Journal of Atomic and Molecular Sciences
VL - 3
SP - 225
EP - 234
PY - 2013
DA - 2013/04
SN - 4
DO - http://doi.org/10.4208/jmas.063012.072912a
UR - https://global-sci.org/intro/article_detail/jams/8254.html
KW - molecular dynamics simulation, cross-correlation matrix, p53-MDM2 interaction, binding free energy, MM-PBSA.
AB - <p style="text-align: justify;">The p53-MDM2 interaction has been an important target of drug design curing cancers. In this work, Molecular dynamics (MD) simulation coupled with molecular mechanics/Poisson Boltzmann surface area method (MM-PBSA) is performed to
calculate binding free energy of peptide inhibitor pDI6W to MDM2. The results show
that van der Waals energy is the dominant factor of the pDI6W-MDM2 interaction.
Cross-correlation matrix calculated suggests that the main motion of the residues in
MMDM2 induced by the inhibitor binding is anti-correlation motion. The calculations
of residue-residue interactions between pDI6W and MDM2 not only prove that five
residues Phe19’, Trp22’, Trp23’, Leu26’ and Thr27’ from pDI6W can produce strong interactions with MDM2, but also show that $CH$-$π,$ $CH$-$CH$ and $π$−$π$ interactions drive
the binding of pDI6W in the hydrophobic cleft of MDM2. This study can provide theoretical helps for anti-cancer drug designs.</p>