were -32.79 kJ/mol and -31.12 kJ/mol, respectively. In contrast, the crystal structure from blind docking exhibited higher average binding affinities of -37.99 kJ/mol for D2 and -34.85 kJ/mol for D3. Similarly, grid-based docking demonstrated even greater average binding affinities of -41.38 kJ/mol for D2 and -40.08 kJ/mol for D3. Our findings suggest that both blind and grid docking outperformed the ensemble docking approach, likely due to the rigidity of the receptor in blind and grid docking, resulting in minimal variations in binding affinity compared to ensemble docking. This indicates a higher likelihood of a specific receptor conformation extracted from snapshots matching those used in grid and blind docking. Overall, our study underscores the importance of considering receptor flexibility in molecular docking studies and highlights the utility of the Relaxed Complex Scheme in elucidating the influence of receptor dynamics on ligand binding affinity.