In order to establish a pathway to evaluate chemical kinetic mechanisms (detailed or reduced) in a real engine environment, a GT Power model of the well-studied Cooperative Fuels Research (CFR) engine was developed and validated against experimental data for primary reference fuel blends between 60 and 100 under RON conditions. The CFR engine model utilizes a predictive turbulent flame propagation sub-model, and implements a chemical kinetic solver to solve the end-gas chemistry. The validation processes were performed simultaneously for thermodynamic and chemical kinetic parameters to match IVC conditions, burn rate, and knock prediction. A recently published kinetic mechanism was implemented in GT-Power, and was found to over-predict the low temperature heat release for iso-octane and PRF blends, leading to advanced knock onset phasing compared to experiments. Three reaction rates in the iso-octane and n-heptane pathways were tuned in the kinetic mechanism in order to match experimental knock-point values, yielding excellent agreement in terms of the knock onset phasing, burn rate, and the thermodynamic conditions compared to experiments. This developed model provides the initial/boundary conditions of the CFR engine under RON conditions, including IVC temperature and pressure, MFB profile, residual fraction and composition. The conditions were then correlated as a function of CFR engine compression ratio, and implemented in a 0-D SI engine model in Chemkin Pro in order to demonstrate an application of the current work. The Chemkin Pro and GT-Power simulations provided nearly identical results despite significant differences in heat transfer models and chemical kinetic solvers. This work provides the necessary framework by which robust chemical kinetic mechanisms can be developed, evaluated, and tuned, based on the knocking tendencies in a real engine environment for PRF blends.