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To address some of the inherent challenges in modeling metalloenzymes, we here report an extension to the functional form of the OPLS3e force field to include terms adopted from the ligand field molecular mechanics (LFMM) model, including the angular overlap and Morse potential terms. The integration of these terms with OPLS3e, herein referred to as OPLS3e+M, improves the description of metal–ligand interactions and provides accurate relative binding energies and geometric preferences of transition-metal complexes by training to gas-phase density functional theory (DFT) energies. For [Cu(H₂O)₄]²⁺, OPLS3e+M significantly improves H₂O binding energies and the geometric preference of the tetra-aqua Cu²⁺ complex. In addition, we conduct free-energy perturbation calculations on two pharmaceutically relevant metalloenzyme targets, which include chemical modifications at varying proximity to the …