Molecular Modeling for Quantitative Analysis of Molecular Interaction†

The binding affinity (log nK) between human serum albumin and acidic drugs was quantitatively analyzed using a computational chemical method with several model phases. A flat guanidino-phase was the most efficient for calculating log nK values, and docking was easily performed. A flowerpot type model phase bonded a guanidino group at the center bottom demonstrating that ion-ion interaction was the main driving force. A large molecule pushed aside the hydrophobic wall of log P = 5, and reached the guanidino group. Ionized acidic compounds may reach the guanidino group inside a protein by ion-ion interaction through a narrow channel of length 10Å.