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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(H 2 O) 4 ] 2+ , OPLS3e+M significantly improves H 2 O binding energies and the geometric preference of the tetra-aqua Cu 2+ complex. In addition, we conduct free-energy perturbation calculations on two pharmaceutically relevant metalloenzyme targets, which include chemical modifications at varying proximity to the binding-site metals, including changes to the metal-binding moiety of the ligand itself. The extensions made to OPLS3e lead to accurate predicted relative binding free energies for these series (mean unsigned error of 1.29 kcal mol -1 ). Our results provide evidence that integration of the LFMM model with OPLS3e can be utilized to predict thermodynamic quantities for such systems near chemical accuracy. With these improvements, we anticipate that robust free-energy perturbation calculations can be employed to accelerate the drug development efforts for metalloenzyme targets.