Binding interaction of a potential statin with β-lactoglobulin: An in silico approach.

This article reports the interaction between a synthetic statin, fluvastatin with bovine milk protein, β -lactoglobulin (BLG) through docking, constant pH molecular dynamics simulation (cpHMD) and binding free energy calculations. Docking provides the best fitted binding mode of the ligand with the receptor. We have carried out MD simulations of the protein and protein-ligand complex at two different pH viz. 7.0 and 1.5. We have found that the protein shows more compact behavior at pH 1.5 and this behavior is more prominent on complexation with the ligand. In support of this we have utilized the properties viz. root mean square deviations, root mean square fluctuations, radius of gyration, protein-ligand hydrogen bond and binding free energy calculations. Calculation of radius of gyration shows that the value decreases from 14.51 Å to 14.03 Å on complexation at pH 1.5. Calculations of hydrogen bonds at pH 1.5 confirms that hydrogen bonding interactions of the binding residues of the protein with the ligand provides stability to the complex. We have used molecular mechanics-generalized Born surface area (MMGBSA) method to estimate binding free energies of the protein with the ligand. MMGBSA calculations suggest that there is favorable binding interactions between the protein and the ligand with major contributions from Van der Waals interactions. We have found that the net average binding free energy is −29.394 kcal/mol that reveals a favorable binding interactions of BLG with the ligand. This study suggests that in spite of the acidic environment in the stomach BLG can act as a carrier for the acid-sensitive drug molecules such as fluvastatin because of its highly stable conformational behavior in the acidic pH. [Display omitted] • CpHMD simulations were employed to set pH at 1.5 of the solutions. • Molecular docking predicts the best fitted binding pose of the protein-drug complex. • Hydrogen bonding and Van der Waals interaction play vital role in complex formation. • Complexation results conformational stability to the protein in acidic pH. • Due to complexation the acid-sensitive drug remains protected in acidic pH. [ABSTRACT FROM AUTHOR]