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

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) x 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. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

The interaction mechanism between protocatechualdehyde (PA) and C-terminal-binding protein 1 (CtBP1) was studied in detail, revealing that PA is a potential inhibitor of CtBP1. Using molecular docking and molecular dynamics simulations, visual molecular recognition models were constructed, demonstrating the stable binding of PA to CtBP1. Experimental results from fluorescence spectroscopy and time-resolved fluorescence spectroscopy confirmed the static quenching mechanism, and the binding constant of the PA-CtBP1 system was determined. Thermodynamic parameters and spectroscopic analysis indicated that the binding of PA to CtBP1 was primarily driven by H-bond interactions and van der Waals forces, resulting in slight changes in the secondary structure of CtBP1.