Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations
文献类型：期刊论文
| 作者 | Chen, Jianzhong1,2; Zhang, Dinglin1; Zhang, Yuxin1; Li, Guohui1 |
| 刊名 | international journal of molecular sciences
 |
| 出版日期 | 2012-02-01 |
| 卷号 | 13期号:2页码:2176-2195 |
| 关键词 | p53-MDM2/MDMX interaction molecular dynamics simulation binding free energy alanine scanning |
| 英文摘要 | inhibition of p53-mdm2/mdmx interaction is considered to be a promising strategy for anticancer drug design to activate wild-type p53 in tumors. we carry out molecular dynamics (md) simulations to study the binding mechanisms of peptide and non-peptide inhibitors to mdm2/mdmx. the rank of binding free energies calculated by molecular mechanics generalized born surface area (mm-gbsa) method agrees with one of the experimental values. the results suggest that van der waals energy drives two kinds of inhibitors to mdm2/mdmx. we also find that the peptide inhibitors can produce more interaction contacts with mdm2/mdmx than the non-peptide inhibitors. binding mode predictions based on the inhibitor-residue interactions show that the p-p, ch-p and ch-ch interactions dominated by shape complimentarity, govern the binding of the inhibitors in the hydrophobic cleft of mdm2/mdmx. our studies confirm the residue tyr99 in mdmx can generate a steric clash with the inhibitors due to energy and structure. this finding may theoretically provide help to develop potent dual-specific or mdmx inhibitors. |
| WOS标题词 | science & technology ; physical sciences |
| 类目[WOS] | chemistry, multidisciplinary |
| 研究领域[WOS] | chemistry |
| 关键词[WOS] | protein-protein interactions ; free-energy calculations ; generalized born model ; particle mesh ewald ; hiv-1 protease ; mdm2 inhibitors ; p53 restoration ; cancer-therapy ; stability ; design |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000300715700057 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/143043]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Dalian Inst Chem Phys, State Kay Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116011, Peoples R China 2.Shandong Jiaotong Univ, Dept Math & Phys, Jinan 250031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Jianzhong,Zhang, Dinglin,Zhang, Yuxin,et al. Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations[J]. international journal of molecular sciences,2012,13(2):2176-2195. |
| APA | Chen, Jianzhong,Zhang, Dinglin,Zhang, Yuxin,&Li, Guohui.(2012).Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations.international journal of molecular sciences,13(2),2176-2195. |
| MLA | Chen, Jianzhong,et al."Computational Studies of Difference in Binding Modes of Peptide and Non-Peptide Inhibitors to MDM2/MDMX Based on Molecular Dynamics Simulations".international journal of molecular sciences 13.2(2012):2176-2195. |
入库方式： OAI收割
来源：大连化学物理研究所
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