Conformational alterations and functional changes of pepsin induced by a novel food supplement tetrahydrocurcumin: Multispectral techniques and computer simulations.

Tetrahydrocurcumin (THC), as a novel food supplement, has generated significant interests for its potential impact on health and nutrition. Pepsin serves as the primary enzyme involved in the digestive mechanism. This research investigated the conformational and functional alterations of pepsin induced by THC using multispectral techniques and computer simulations. The results showed that THC enters the cavity of pepsin, in which hydrophobic forces play a major role. The binding constant is 1.044 × 10 4  M -1 at 310 K. The upregulation or downregulation effect of THC on pepsin activity depends on its concentration. Molecular docking outcomes indicated that THC was encapsulated by various amino acids and established H-bonds with Tyr189 and Ser294, revealing that hydrogen bonds also contribute to maintaining the stability of THC-pepsin complex. In addition, the altered activity of pepsin may be related to the interaction between THC and the amino acids at the active site (Asp32) according to energy contribution results. 3D fluorescence spectroscopy, CD spectra and molecular dynamic simulations show that THC causes conformational changes in pepsin. The existence of THC makes pepsin structure to be less dense, leading to the decrease of energy traps. This suggests that pepsin becomes conformationally more suitable to bind to THC.