Volume 4, Issue 3
Insight into Interaction Mechanism of the Inhibitor pDI6W with MDM2 Based on Molecular Dynamics

Jianzhong Chen, Zhi-Qiang Liang, Qing-Gang Zhang, Xiao-Yang Liu, Wei Wang & Jin-Qing Liu

J. At. Mol. Sci., 4 (2013), pp. 225-234.

Published online: 2013-04

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  • Abstract

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.

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COPYRIGHT: © Global Science Press

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chenjianzhong1970@163.com (Jianzhong Chen)

zjxuwangwei@163.com (Wei Wang)

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@Article{JAMS-4-225, author = {Chen , JianzhongLiang , Zhi-QiangZhang , Qing-GangLiu , Xiao-YangWang , Wei and Liu , Jin-Qing}, title = {Insight into Interaction Mechanism of the Inhibitor pDI6W with MDM2 Based on Molecular Dynamics}, journal = {Journal of Atomic and Molecular Sciences}, year = {2013}, volume = {4}, number = {3}, pages = {225--234}, abstract = {

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.

}, issn = {2079-7346}, doi = {https://doi.org/10.4208/jmas.063012.072912a}, url = {http://global-sci.org/intro/article_detail/jams/8254.html} }
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 -

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.

Jianzhong Chen, Zhi-Qiang Liang, Qing-Gang Zhang, Xiao-Yang Liu, Wei Wang & Jin-Qing Liu. (2020). Insight into Interaction Mechanism of the Inhibitor pDI6W with MDM2 Based on Molecular Dynamics. Journal of Atomic and Molecular Sciences. 4 (3). 225-234. doi:10.4208/jmas.063012.072912a
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