Article Highlights:

Unraveling the intricacies of ADH, our study tackles the challenging task of desymmetrizing substituted cyclopentane-1,3-dione through the computational chemistry method. The elusive nature of the metal-independent ADH reaction mechanism is explored, providing valuable insights into its enigmatic workings.

Key Findings:

1. Molecular dynamics simulations disclosed the origin of enantioselectivity, attributing it to the dynamic behavior of the loop 191-205 shaping the binding pocket.

2. QM/MM calculations elucidated the reaction mechanism of LbADH, correlating with our experimental observations.

Significance:

Our research opens new avenues for the rational engineering of ADH, aiming to achieve stereodivergent stereoisomer products. This breakthrough contributes to the broader understanding of enzymatic processes and their potential applications.

Read the full article here! (DOI: 10.1039/D3CP04019D)