This project aims to elucidate the catalytic mechanisms of two halogenases and investigate how active-site mutations influence substrate recognition, enzyme dynamics, and catalytic activity. The study combines molecular dynamics (MD) simulations, enhanced sampling approaches, and QM/MM calculations to investigate enzyme-substrate interactions and catalytic reaction pathways at both atomistic and electronic levels. Initially, approximately 12–20 protein systems will be studied, including wild-type enzymes and rationally engineered variants. Additional variants may be generated iteratively based on experimental findings and computational results. Long-timescale MD simulations will be used to characterize substrate binding, conformational dynamics, and active-site rearrangements. Enhanced sampling methods such as metadynamics and umbrella sampling will be employed when necessary to explore free-energy landscapes and rare catalytic events. Representative structures obtained from MD simulations will subsequently be subjected to QM/MM calculations using ORCA and/or CP2K to investigate reaction mechanisms, transition states, and activation barriers. The computational results will complement ongoing experimental studies involving mutagenesis and enzymatic characterization, providing mechanistic insights that support future enzyme engineering and biocatalyst development.