The Dynamic Theozyme Model: A New Strategy for the Study of Enzyme Catalysis

ABSTRACT

The dynamic interactions between enzymes and substrates, as well as the accurate elucidation of enzymatic catalytic mechanisms, are key scientific questions in modern enzymology. The development of quantum chemical calculation methods provides a new technical means for the study of enzymatic catalytic mechanisms. Among these, the theozyme model can enormously simplify the required computations and has become an important method for exploring enzymatic catalysis. However, as catalytic reactions discovered grow increasingly complex, the theozyme model built from static structures is increasingly found to be inadequate for accurate explanations of catalytic mechanisms. We have now coupled molecular dynamics (MD) simulations with the theozyme model to create a dynamic theozyme model for the study of complex catalytic systems. The new strategy utilizes MD simulations of transition states or key intermediates to obtain structural information during catalysis, providing reliable guidance for constructing the theozyme model. We have applied this strategy to several distinct catalytic systems, successfully revealing catalytic mechanisms leading to regioselectivity and stereoselectivity. The strategy proposed herein effectively integrates dynamic interaction analysis with quantitative mechanism evaluation, providing a research paradigm that balances accuracy and efficiency for elucidating enzymatic catalytic mechanisms.

This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics