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
相关论文
共 50 条
  • [41] Decoding molecular mechanism underlying binding of drugs to HIV-1 protease with molecular dynamics simulations and MM-GBSA calculations
    Yu, Y. X.
    Liu, W. T.
    Li, H. Y.
    Wang, W.
    Sun, H. B.
    Zhang, L. L.
    Wu, S. L.
    SAR AND QSAR IN ENVIRONMENTAL RESEARCH, 2021, 32 (11) : 889 - 915
  • [42] Molecular Docking, Molecular Dynamics Simulations, and Free Energy Calculation Insights into the Binding Mechanism between VS-4718 and Focal Adhesion Kinase
    Shi, Mingsong
    Chen, Tao
    Wei, Siping
    Zhao, Chenyu
    Zhang, Xinyu
    Li, Xinghui
    Tang, Xinyi
    Liu, Yan
    Yang, Zhuang
    Chen, Lijuan
    ACS OMEGA, 2022, : 32442 - 32456
  • [43] Exploring the Binding Mechanism of PF-07321332 SARS-CoV-2 Protease Inhibitor through Molecular Dynamics and Binding Free Energy Simulations
    Ahmad, Bilal
    Batool, Maria
    ul Ain, Qurat
    Kim, Moon Suk
    Choi, Sangdun
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (17)
  • [44] Relationship between helix stability and binding affinities: molecular dynamics simulations of Bfl-1/A1-binding pro-apoptotic BH3 peptide helices in explicit solvent
    Modi, Vivek
    Lama, Dilraj
    Sankararamakrishnan, Ramasubbu
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2013, 31 (01): : 65 - 77
  • [45] Dissecting the CRISPR Cas1-Cas2 Protospacer Binding and Selection Mechanism by Using Molecular Dynamics Simulations
    School of Science, Chongqing University of Posts and Telecommunications, Chongqing
    400065, China
    不详
    325001, China
    不详
    CA
    92697, United States
    J Phys Chem B, 15 (3563-3574):
  • [46] Effects of Lys to Glu mutations in GsMTx4 on membrane binding, peptide orientation, and self-association propensity, as analyzed by molecular dynamics simulations
    Nishizawa, Kazuhisa
    Nishizawa, Manami
    Gnanasambandam, Radhakrishnan
    Sachs, Frederick
    Sukharev, Sergei I.
    Suchyna, Thomas M.
    BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2015, 1848 (11): : 2767 - 2778
  • [47] Dissecting the CRISPR Cas1-Cas2 Protospacer Binding and Selection Mechanism by Using Molecular Dynamics Simulations
    Zheng, Chuanbo
    Liang, Hongqiong
    Dai, Liqiang
    Yu, Jin
    Long, Chunhong
    JOURNAL OF PHYSICAL CHEMISTRY B, 2024, 128 (15): : 3563 - 3574
  • [48] Evaluation of transport mechanism of ascorbic acid through cyclic peptide-based nanotubes: A molecular dynamics study
    Joozdani, Farzane Abasi
    Taghdir, Majid
    JOURNAL OF MOLECULAR LIQUIDS, 2022, 349
  • [49] Molecular dynamics simulations of human glutathione transferase P1-1: Analysis of the induced-fit mechanism by GSH binding
    Stella, L
    Nicotra, M
    Ricci, G
    Rosato, N
    Di Iorio, EE
    PROTEINS-STRUCTURE FUNCTION AND GENETICS, 1999, 37 (01): : 1 - 9
  • [50] Computational modeling of cyclic peptide inhibitor-MDM2/MDMX binding through global docking and Gaussian accelerated molecular dynamics simulations
    Wang, Yeng-Tseng
    Cheng, Tian-Lu
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2021, 39 (11): : 4005 - 4014