A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations

被引:0
|
作者
Liu, Senchen [1 ]
Hao, Xiafei [2 ]
Miao, Dongqiang [1 ]
Zhang, Yanjun [1 ]
机构
[1] Hebei Univ Engn, Sch Math & Phys, Handan 056038, Peoples R China
[2] Hebei Univ Engn, Med Coll, Handan 056038, Peoples R China
来源
JOURNAL OF PHYSICAL CHEMISTRY B | 2024年 / 128卷 / 38期
基金
中国国家自然科学基金;
关键词
CONTINUUM SOLVENT; FREE-ENERGIES; PROTEIN; RNA; VISUALIZATION; COACTIVATOR; PREDICTION; STABILITY; ALGORITHM; INSIGHTS;
D O I
10.1021/acs.jpcb.4c02325
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Metastasis of breast cancer is the main cause of death for patients with breast cancer. The interaction between metadherin (MTDH) and staphylococcal nuclease domain 1 (SND1) plays a pivotal role in promoting breast cancer development. However, the binding details between MTDH and SND1 remain unclear. In this study, we employed all-atom molecular dynamics simulations (MDs) and conducted binding energy calculations to investigate the binding details and the impact of key residue mutations on binding. The mutations in key residues have not significantly affected the overall stability of the structure and the fluctuation of residues near the binding site; they have exerted a substantial impact on the binding of SND1 and MTDH peptide. The electrostatic interactions and van der Waals interactions play an important role in the binding of SND1 and the MTDH peptide. The mutations in the key residues have a significant impact on electrostatic and van der Waals interactions, resulting in weakened binding. The energy contributions of key residues mainly come from the electrostatic energy and van der Waals interactions of the side chain. In addition, the key residues form an intricate and stable network of hydrogen bonds and salt-bridge interactions with the MTDH peptide. The mutations in key residues have directly disrupt the interactions formed between SND1 and MTDH peptide, consequently leading to changes in the binding mode of the MTDH peptide. These analyses unveil the detailed atomic-level interaction mechanism between SND1 and the MTDH peptide, providing a molecular foundation for the development of antibreast cancer drugs.
引用
收藏
页码:9074 / 9085
页数:12
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