Computational Study of Terahertz-Induced Phase Transitions at Molecular Interfaces

Structural phase transitions driven by atomic rearrangements at the interaction interfaces of biological macromolecules, particularly proteins, are fundamental to regulating critical physiological processes, making their effective modulation key to developing targeted therapeutics. Existing induction strategies encounter substantial limitations: Chemical methods have difficulty accessing shallow binding pockets and can lead to invasive, irreversible modifications, while common visible and near-infrared modulation technologies are hindered by side effects induced by exogenous agents and restricted deep-tissue penetration. Here, using molecular dynamics simulations of the programmed cell death protein 1/programmed cell death 1 ligand 2 complex, we find terahertz light (40.2 THz) to be a reversible, nonthermal, and noninvasive physical induction modality to drive a directed structural phase transition. Energetic analyses reveal that the terahertz field markedly decreases the binding affinity by more than 3-fold and reduces the free energy barrier by nearly 3-fold. Fundamentally, our research demonstrates that this directed decoupling process originates from the coherent resonance of certain key interfacial residues. Collectively, our findings propose a universal physical strategy to modulate macromolecular interfaces, providing an essential computational framework to guide future experimental validations in noninvasive tumor immunotherapy.