Investigating the Interaction Mechanism of CAT-BT-Br and Key Residue Mutations for Castration-Resistant Prostate Cancer through Molecular Dynamics Simulation

Prostate cancer is the second most common cancer in men, second only to lung cancer. Castration-resistant prostate cancer (CRPC) was formerly known as hormone-resistant prostate cancer. The aim of this study is to reveal the effect of key residue mutations on the binding mechanism between catalase (CAT) and benzaldehyde thiourea derivatives (BT-Br), providing theoretical support for the development of novel CAT inhibitors. This article analyzes the structural stability, binding energy and decomposition, hydrogen bonding, etc. of wild-type (WT) and multiple mutations systems. The results showed that, in addition to the R203A mutant, all mutation systems significantly enhanced the binding ability of CAT to BT-Br, and their binding free energy contribution mainly came from van der Waals interactions. Hydrogen bond analysis shows that the hydrogen bond occupancy rate of the WT system is relatively low, while mutations such as V302A have a hydrogen bond occupancy rate as high as 93.05%, indicating a significant enhancement in their binding ability. In addition, mutations have limited impact on the overall stability of proteins, but some mutations such as Y215A and V302A significantly alter the binding site and direction of proteins. The results of principal component analysis (PCA) in other systems are consistent with those of root mean square fluctuation (RMSF) analysis, and the binding site shows little movement. This study not only elucidates the microscopic effects of key residue mutations on the binding mechanism between CAT and BT-Br but also provides new targets and drug design ideas for prostate cancer treatment based on iron death induction strategies.