A Study on the\nBinding Mechanism and the Impact of\nKey Residue Mutations between SND1 and MTDH Peptide through Molecular\nDynamics Simulations

Metastasis of breast cancer is the main cause of death\nfor patients\nwith breast cancer. The interaction between metadherin (MTDH) and\nstaphylococcal nuclease domain 1 (SND1) plays a pivotal role in promoting\nbreast cancer development. However, the binding details between MTDH\nand SND1 remain unclear. In this study, we employed all-atom molecular\ndynamics simulations (MDs) and conducted binding energy calculations\nto investigate the binding details and the impact of key residue mutations\non binding. The mutations in key residues have not significantly affected\nthe overall stability of the structure and the fluctuation of residues\nnear the binding site; they have exerted a substantial impact on the\nbinding of SND1 and MTDH peptide. The electrostatic interactions and\nvan der Waals interactions play an important role in the binding of\nSND1 and the MTDH peptide. The mutations in the key residues have\na significant impact on electrostatic and van der Waals interactions,\nresulting in weakened binding. The energy contributions of key residues\nmainly come from the electrostatic energy and van der Waals interactions\nof the side chain. In addition, the key residues form an intricate\nand stable network of hydrogen bonds and salt-bridge interactions\nwith the MTDH peptide. The mutations in key residues have directly\ndisrupt the interactions formed between SND1 and MTDH peptide, consequently\nleading to changes in the binding mode of the MTDH peptide. These\nanalyses unveil the detailed atomic-level interaction mechanism between\nSND1 and the MTDH peptide, providing a molecular foundation for the\ndevelopment of antibreast cancer drugs.