The quantum revolution in enzymatic chemistry: combining quantum and classical mechanics to understand biochemical processes

Abstract This paper reflects the authors’ personal journey in applying quantum chemistry methods to understand one of the most important processes in nature: enzymatic catalysis. The integration of quantum mechanics with biomolecular simulations represents one of the most significant advances in computational enzymology over the past few decades. This approach has revolutionized our understanding of enzyme function and catalytic mechanisms, and has provided powerful tools for enzyme design and optimization. Combined quantum mechanics/molecular mechanics (QM/MM) methods have transformed theoretical studies of enzymatic reactions from qualitative descriptions to quantitative predictions, capable of guiding experimental work with unprecedented accuracy.