Simulation-guided relationships and interaction characteristics of human CtBP1 in complex with protocatechualdehyde

Abstract

• Quenching mechanism of PA to CtBP1 is static quenching with moderate affinity. • Hydrogen bond and van der Waals force are the main binding forces. • The amino acids of CtBP1, Try318, plays a key role in the interaction. • Binding induces conformational changes in CtBP1 after interaction. The mechanism of interaction of protocatechualdehyde (PA) to C-terminal-binding protein 1 (CtBP1) was studied in detail from a new perspective, and it was verified that PA was a potential inhibitor of CtBP1. Visual molecular recognition models were built based on molecular docking and molecular dynamics (MD) simulations, and it was shown that PA can bind to CtBP1 stably. The static quenching mechanism was confirmed by fluorescence spectroscopy and time-resolved fluorescence spectroscopy, indicating that the binding constant of the PA-CtBP1 system at a single binding site was approximately (5.291 ± 0.204) × 10 4 L/mol at 298 K . The thermodynamic parameters showed that the binding of PA to CtBP1 was mainly initiated by H-bond interactions and van der Waals forces. Circular dichroism (CD) and Fourier-Transform Infrared (FT-IR) spectroscopy manifested that the secondary structure of CtBP1 had slightly changed. This work clarified the research progress of the specific binding mechanism of PA and CtBP1 from the molecular level, which provided new insight into the pharmacological effects of PA.