The curated CSAR-NRC benchmark sets provide valuable opportunity for testing or comparing the performance of both existing and novel scoring functions. We apply two different scoring functions, both independently and in combination, to predict binding affinity of ligands in the CSAR-NRC datasets. One, reported here for the first time, employs multiple chemical-geometrical descriptors of the protein-ligand interface to develop Quantitative Structure – Binding Affinity Relationships (QSBAR) models; these models are then used to predict binding affinity of ligands in the external dataset. Second is a physical force field-based scoring function, MedusaScore. We show that both individual scoring functions achieve statistically significant prediction accuracies with the squared correlation coefficient (R2) between actual and predicted binding affinity of 0.44/0.53 (Set1/Set2) with QSBAR models and 0.34/0.47 (Set1/Set2) with MedusaScore. Importantly, we find that the combination of QSBAR models and MedusaScore into consensus scoring function affords higher prediction accuracy than any of the contributing methods achieving R2 of 0.45/0.58 (Set1/Set2). Furthermore, we identify several chemical features and non-covalent interactions that may be responsible for the inaccurate prediction of binding affinity for several ligands by the scoring functions employed in this study