Knock is a major bottleneck to achieving higher efficiency in Spark-Ignition (SI) engines. The recent trends of boosting, downsizing and downspeeding have exacerbated this issue by driving engines toward higher power density and higher load duty cycles. Apart from the engine operating conditions, fuel anti-knock quality is a major determinant of the knocking tendency in engines, as quantified by its octane number (ON). The ON of a fuel is based on an octane scale which is defined according to the standard octane rating methods for Research Octane Number (RON) and Motor Octane Number (MON). These tests are performed in a single cylinder Cooperative Fuel Research (CFR) engine. In the present work, a virtual CFR engine model based on 3D computational fluid dynamics (CFD) was developed. The knock model employed the G-equation approach to track the propagating turbulent flame front and a homogeneous reactor multi-zone model was used to capture auto-ignition in the end-gas ahead of the flame front. The G-equation model, in particular, was extended by implementing a tabulated laminar flame speed approach instead of using empirical correlations. Multi-cycle RANS simulations were performed for both knocking (RON condition) and non-knocking (retarded spark timing) operating points for iso-octane fuel. A 165-species skeletal mechanism for gasoline blend surrogates was employed to incorporate fuel chemistry effects and to generate the laminar flame speed look up table. The engine valve lift profiles, intake/exhaust pressures and in-cylinder pressure data for model validation, were obtained from experiments performed in an in-house CFR engine. In addition, a well calibrated 1D GT-Power model provided the necessary wall temperatures and residual gas fraction information for the CFD simulations. It was demonstrated that the CFD setup along with the proposed combustion modeling strategy was capable of predicting the combustion characteristics with good accuracy, for normal SI combustion as well as knocking combustion. The virtual CFR engine model can, therefore, serve as an effective numerical tool to study fuel property effects on knock propensity at different engine operating conditions.