Electric field induced the changes in structure and function of human transforming growth factor beta receptor type I: from molecular dynamics to docking

Abstract

The transforming growth factor beta (TGF-β) signaling pathway is believed to play essential roles in several physiological activities, including cancer. TGF-β receptor type I (TBR-I) is a key membrane receptor protein in the TGF-β signaling pathway, which relates to many intracellular biological effects. In recent years, cold atmospheric plasma (CAP) has been found to have promising prospects in selective anticancer therapy and has confirmed its essential role in the TGF-β signaling pathway. However, the ambiguous effect of CAP-induced electric field (EF) on TBR-I still limits the application of CAP in clinical therapy. Molecular dynamics is applied to assess the effect of EF on the structure of the extracellular domain of TBR-I using a series of indicators and methods, and then we discuss the ligand binding ability of TBR-I. Results show that moderate EF intensities’ structural restraints may contribute to the structural stability and ligand-binding ability of TBR-I, but an EF higher than 0.1 V/nm will be harmful. What’s more, EF induces a change in the docking interface of TBR-I, showing the conformation and position of special sequences of residues decide the ligand binding surface. The relevant results suggest that CAP-induced EF plays a crucial role in receptor-receptor interaction and provides significant guidelines for EF-related anticancer therapy.

Communicated by Ramaswamy H. Sarma

Keywords:

• Transforming growth factor receptor
• molecular dynamics
• conformational change
• electric field
• molecular docking

Acknowledgments

This research was supported by HPC Platform of Xi’an Jiaotong University. This work was supported by [the Natural Science Basic Research Program of Shaanxi Province] under Grant [number 2023-JC-YB-004]; [Key Research and Development Program of Shaanxi] under Grant [number 2024SF-YBXM-386]; [Natural Science Basic Research Plan in Shaanxi Province of China] under Grant [number 2022JM-404]; and [the Fundamental Research Funds for the Central Universities, CHD] under Grant [numbers 300102383103, 300102383203].

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.