Dynamics of Sqle under electric field exposure

Squalene epoxygenase (Sqle) serves as an FDA-approved anti-tumor target, with its expression down-regulated following exposure to direct current electric fields. However, the underlying mechanisms remain unclear. This study investigates the structural modifications of Sqle proteins under a range of electric field intensities (0 V/nm ≤ E ≤ 1 V/nm) using molecular dynamics (MD) simulations. Structural changes were assessed using metrics such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), hydrogen bond dynamics, dipole moment, and alterations in secondary structure. Our findings reveal that electric fields destabilize the Sqle protein structure, resulting in the unwinding of stable α-helices and β-folds into an unstable coil configuration. A linear relationship was observed between structural unwinding and electric field intensity, with increased RMSD values indicating significant conformational changes under stronger electric fields. Additionally, electric fields promote Sqle protein flexibility while reducing hydrogen bond count, and the total dipole moment increases with electric field strength. These insights enhance our understanding of Sqle's role in tumor treatment influenced by electric fields, potentially paving the way for novel therapeutic applications.